Conditioned Withdrawal Research Articles

DEVELOPMENT PROSPECTS OF LONDON AS THE WORLD’S FINANCIAL CENTER IN THE CONDITIONS OF BREXIT

The purpose of the study is to examine the role of London as the global financial center in the modern international financial system under the conditions of Britain's withdrawal from the European Union. Methodology. During the study, the comparative method, methods of statistics and economic-mathematical modeling were used. The methodological and theoretical basis of the study is the fundamental provisions of international economic relations, the study of economists in the field of international monetary and financial relations. Information basis is analytical reports of international financial centers and statistical databases of international organizations. Results. Nowadays, London has all the necessary factors for success: open economy, developed financial infrastructure, stability of taxation system, geographical location, long-term government support, transparent policy, investor diversity and multi-culture. It is revealed that a growing variety of financial instruments is a characteristic feature of London as a modern global financial center. As a result, London is gradually winning the battle for the title of the world's leading financial center. The Government of the United Kingdom constantly develops growth strategies of the City of London, creates favorable conditions for the work of international companies, and attracts highly qualified specialists from other countries in the field of finance and law. The competent policy of the state and the wide range of services provided for the successful transactions on stock exchanges and commodity markets help London to maintain undisputed leadership in the global financial market and minimize losses associated with Brexit. At the same time, the decision of the UK to withdraw from the EU had a negative impact on the stability of the country's banking system, it had provoked a decline in the country's credit ratings, a drop in the pound sterling against the dollar and the euro. Another problem for the City of London was the speculation around the loss of multinational companies that might prefer Frankfurt, after the completion of the UK's exit from the EU. Regression analysis revealed that the FTSE 100 index is influenced by such indicators: the industrial production index, the short-term interest rate and the money supply. It was revealed that the current stability of the UK financial system is related to the yield of government securities: a decrease in yield leads to an increase in the stability of the financial system. Practical implications. The study showed that London still remains the most significant financial center in the world, despite concerns about the massive loss of investors and capital as a result of Brexit. In the future, one can expect a strengthening of the pound sterling and higher policy of the Bank of England than in the euro zone, increase of interest rates and a reduction in the tax rates, due to the final withdrawal from the EU, the UK government will no longer have to meet the Maastricht criteria. On the other hand, the UK is not going to enter the EU Banking Union, which will maintain a fairly high level of liberalization in the country's banking system. All this, in turn, will make London even more attractive for national and foreign investors. Value. The role and place of London in the modern global economy and the interest of investors from different countries in the City of London determine the value of this research in the context of the current development of the global financial market and the possible consequences of Brexit, which in the long run are mostly positive.

Cue-induced nicotine-seeking behavior after withdrawal with or without extinction in rats.

Exposure to smoking-associated environmental cues during smoke cessation elicits self-reported urge/craving to smoke, which precipitates relapse even after prolonged abstinence. Incubation of cue-induced cigarettes craving during abstinence has been observed in human smokers recently. The present studies assessed cue-induced nicotine-seeking behavior under different withdrawal conditions in rats with a history of nicotine self-administration. We found that non-reinforced operant responding during cue-induced nicotine seeking after different periods of withdrawal from nicotine exhibited an inverted U-shaped curve, with higher levels of responding after 7-21 days of withdrawal than those after 1-day withdrawal. Cue-induced nicotine-seeking responding is long lasting and persists even after 42 days of forced withdrawal in the home cages. Interestingly, repeated testing of cue-induced nicotine seeking at different withdrawal time points (1, 7, 14, 21 and 42 days) in the same individual alleviated responding as compared with the between-subjects assessment. Furthermore, extinction training during nicotine withdrawal significantly decreased cue-induced reinstatement of nicotine-seeking behavior. Together, profound time-dependent incubation of cue-induced craving in nicotine-experienced rats were observed. In addition, repeated cue exposure or extinction training decreases cue-induced craving. The demonstration of incubation of nicotine craving phenomenon in both rat and human studies provides support for the translational potential of therapeutic targets for relapse uncovered through mechanism studies in rats.

Experimental study on the vertical deformation of aquifer soils under conditions of withdrawing and recharging of groundwater in Tongchuan region, China

Land subsidence due to aquifer-system compaction accompanying groundwater extraction is a global hazard. Rising urban construction and groundwater demand necessitate increased awareness and better understanding of the geological problem. Motivated by the lack of laboratory-scale studies on this issue, an experimental investigation on the newly developed Tongchuan region, China, is presented. The study addresses the deformation behaviors of three soil samples, with the lithology of silty clay, silt, and fine sand, under the conditions of groundwater withdrawal and recharge using the GDS Consolidation Testing System. Results indicate that all three samples were characterized by elastic–plastic deformation under the conditions of withdrawing and recharging. The vertical deformation of the silty clay in the aquitard above the first confined aquifer was larger than those of the other two samples, and its deformation is a gradual and long process; thus, considerable attention should be paid to deformation in this aquitard due to the apparent creep effect and tiny rebound deformation. However, the settlement of the fine sand in the second confined aquifer cannot be ignored due to the great thickness of the aquifer. For the same soil, as the pore-water pressure declined, the unit rate of vertical deformation decreased gradually, whereas the creep effect of deformation in the later declining stage of pore-water pressure was more apparent than that in the former declining stage. These observations are highly important to the local government, which is developing measures to prevent and control subsidence.

Validation of GRACE based groundwater storage anomaly using in-situ groundwater level measurements in India

In this study, we tried to validate groundwater storage (GWS) anomaly obtained from a combination of GRACE and land-surface model based estimates, for the first time, with GWS anomaly obtained from a dense network of in-situ groundwater observation wells within 12 major river basins in India. We used seasonal data from >15,000 groundwater observation wells between 2005 and 2013, distributed all over the country. Two recently released GRACE products, RL05 spherical harmonics (SH) and RL05 mascon (MS) products are used for comparison with in-situ data. To our knowledge, this is the first study of comparing the performance of two independent GRACE products at a sub-continental scale. Also for the first time, we have created a high resolution (0.10×0.10) map of specific yield for the entire country that was used for calculating GWS. Observed GWS anomalies have been computed using water level anomalies and specific yield information for the locale of individual observation wells that are up-scaled to basin-scale in order to compare with GRACE-based estimates. In general GRACE-based estimates match well (on the basis of the statistical analyses performed in the study) with observed estimates in most of the river basins. On comparing with observed GWS anomaly, GRACE-SH estimates match well in terms of RMSE, while GRACE-MS estimates show better association in terms of correlation, while the output of skewness, kurtosis, coefficient of variation (CV) and scatter analyses remain inconclusive for inter-comparison between two GRACE estimates. We used a non-parametric trend estimation approach, the Hodrick-Prescott (HP) filter, to further assess the performance of the two GRACE estimates. GRACE-MS estimates clearly outperform GRACE-SH estimates for reproducing observed GWS anomaly trends with significantly (>95% confidence level) strong association in 10 out of 12 basins for GRACE-MS estimates, on the other hand, GRACE-SH estimates show significantly (>95% confidence level) strong association in 6 out of 12 basins. On the basis of the study output, we recommend using GRACE-MS estimates for groundwater studies over the region and other regions of the globe with similar climatic, hydrogeologic or groundwater withdrawal conditions.

The middle-aged ovariectomized marmoset (Callithrix jacchus) as a model of menopausal symptoms: Preliminary evidence

Menopausal women often suffer from hot flashes and sleep disturbances that significantly impact their quality of life. Both human and animal studies suggest that loss of estrogens during menopause contribute to these symptoms. In the female rat, both core body temperature (CBT) and sleep are sensitive to 17β-estradiol (E2) levels, but important differences between the rat and the human patterns limit the interpretation of the results. The sleep and thermoregulation of the common marmoset (Callithrix jacchus) more closely resemble human patterns. However, no study to date has examined whether E2 influences sleep and thermoregulation in this species. The main goal of the present study was to investigate the suitability of the ovariectomized (OVX) marmoset for studying two major menopausal symptoms experienced by women, sleep disturbance and thermodysregulation. Two middle-aged OVX marmosets (6years old) were implanted with a telemeter that records electroencephalograms (EEG), electromyograms (EMG), and CBT. Sleep patterns and CBT were recorded under baseline, two E2 replacement (6 and 12μg/kg/day, p.o.) conditions and two E2 withdrawal conditions. Relative to both baseline and withdrawal, high E2 replacement was associated with lower nighttime CBT. In addition, fewer nighttime arousals were observed under low E2 replacement compared to baseline. Higher delta power was observed under both E2 replacement conditions suggesting enhanced sleep quality. These preliminary results suggest that E2 modulates sleep and thermoregulation in the OVX marmoset, making it a promising model for studying menopausal symptoms.

Activation of dura-sensitive trigeminal neurons and increased c-Fos protein induced by morphine withdrawal in the rostral ventromedial medulla.

Aims Overuse of medications used to treat migraine headache can increase the frequency of headaches. Sudden abstinence from migraine medication can also lead to a period of withdrawal-induced headaches. The aim of this study was to examine the effect of morphine withdrawal localized to the rostral ventromedial medulla (RVM) on the activity of dura-sensitive spinal trigeminal nucleus caudalis (Vc) neurons. Methods Rats were implanted with either morphine or placebo pellets for six to seven days before the microinjection of naloxone methiodide or phosphate-buffered saline into the RVM in urethane-anesthetized animals. Dura-sensitive neurons were recorded in the Vc and the production of c-Fos-like immunoreactivity was quantified. Results In chronic morphine-treated animals, naloxone methiodide microinjections produced a significant increase both in ongoing and facial heat-evoked activity and an increase in Fos-positive neurons in the Vc and in the nucleus reticularis dorsalis, a brainstem region involved in diffuse noxious inhibitory controls. Conclusions These results indicate that activation of pronociceptive neurons in the RVM under conditions of morphine withdrawal can increase the activity of neurons that transmit headache pain. Modulation of the subnucleus reticularis dorsalis by the RVM may explain the attenuation of conditioned pain modulation in patients with chronic headache.

Analysis of Slider Dynamics Considering the Mechanical Spacing in the Slider-Lubricant Contact Regime

This paper analyzed the effect of lubricant contact on slider dynamics under the unsteady proximity condition, which is related to the intermolecular forces between the slider and disk. To investigate the slider dynamics, an experiment was conducted with a commercial drive, and the slider dynamics were analyzed during touch-down and takeoff (TO) considering the approach and withdrawal speeds of the slider. The instability of the slider dynamics increased under the rapid withdrawal condition during TO.

The Effects of Glutamine Supplementation on Markers of Autophagy and Apoptosis in Peripheral Blood Mononuclear Cells from Patients with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a hemoglobinopathy associated with an increased risk of pulmonary hypertension (PH) due to a number of mechanisms that includes iron overload, hemolysis, erythrocyte-derived arginase (which limits both nitric oxide and arginine bioavailability), functional splenectomy, and a hypercoagulable state among others. Glutathione (GSH, and its oxidized pair glutathione disulfide GSSG) is the principal thiol redox buffer in erythrocytes, which has been linked to hemolysis when depleted. Glutamine is not only a precursor to GSH, but also plays an anti-oxidant role through preservation of the intracellular nicotinamide adenine dinucleotide (NAD) levels, required for reducing GSSG back to GSH, thus decreasing the risk for hemolysis. Low erythrocyte glutamine levels are associated with risk of PH as defined by a tricuspid regurgitant jet velocity of (TRV) ≥2.5 m/s measured by Doppler echocardiography. SCD also exhibits an elevated level of circulating leukocytes, known as leukocytosis, which may contribute to vascular occlusion. The mechanism by which leukocytosis occurs is currently unknown. However, leukocyte cell death can be informative on the regulation of leukocyte cell numbers and measurement of mitochondrial BAX and caspase 9, are classic indicators of an active intrinsic cell death pathway. Autophagy is responsible for the turnover of macromolecules and organelles via the lysosomal degradative pathway. In this pathway, LC3 is important for the maturation and transport of autophagosomes and therefore, a reflection of autophagic activity. Autophagy ensures cell survival under certain conditions of nutrient deprivation or growth factor withdrawal and has also been implicated in innate and adaptive immune responses. In this study, the mitochondrial apoptotic marker BAX and the autophagy marker LC3 were examined in a SCD trial of glutamine therapy in patients at risk for PH.Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples taken from SCD (n=13) and control patients (n=7) and BAX and LC3 were measured via western blot analysis. Western blot results were evaluated via densitometry. SCD patients with PH-risk were treated with oral L-glutamine supplementation (10 mg TID) with the objective of estimating the level of cell death and autophagy proteins in circulating PBMCs from SCD patients at baseline and after glutamine supplementation. SCD patients were sampled at baseline (BL),and then at two weeks (W2), four weeks (W4), six weeks (W6), and eight weeks (W8) during the glutamine therapy.Results: Mean age for patients with SCD was 46±14; 39% were male with 54% having Hb-SS, while 46% had Hb-SC. Mean TRV was 3.0±0.6 m/s. The mean age for controls was 32± 12 and 57% were male; all controls were Hb-AA with a mean TRV of 1.8±0.6. At baseline there was no statistical difference in BAX expression between control and SCD patients. In comparison to baseline, however, supplementation with glutamine in SCD patients resulted in significantly increased expression of BAX in PMBCs by 15% over the 8 weeks of therapy; potentially indicating a restorative effect of glutamine on the intrinsic mitochondrial apoptotic pathway, which may ultimately reduce leukocytosis. In contrast, glutamine supplementation over 8 weeks, significantly reduced LC3 expression by 42% in PBMCs, suggesting a decrease in cellular autophagy, thus reducing the ability for PBMCs to remain in circulation.Conclusions: At baseline there was no difference in BAX expression between control and SCD patients, however, after 8 weeks of glutamine supplementation, PBMCs had an increased BAX expression and a decreased LC3 expression. This suggests that PBMCs from glutamine supplemented SCD patients may lose their ability to remain in circulation via apoptosis upregulation and autophagy downregulation DisclosuresWalter:Novartis: Research Funding.

Heroin delay discounting: Modulation by pharmacological state, drug-use impulsivity, and intelligence.

Delay discounting (DD) refers to how rapidly an individual devalues goods based on delays to receipt. DD usually is considered a trait variable but can be state dependent, yet few studies have assessed commodity valuation at short, naturalistically relevant time intervals that might enable state-dependent analysis. This study aimed to determine whether drug-use impulsivity and intelligence influence heroin DD at short (ecologically relevant) delays during two pharmacological states (heroin satiation and withdrawal). Out-of-treatment, intensive heroin users (n = 170; 53.5% African American; 66.7% male) provided complete DD data during imagined heroin satiation and withdrawal. Delays were 3, 6, 12, 24, 48, 72, and 96 hours; maximum delayed heroin amount was thirty $10 bags. Indifference points were used to calculate area under the curve (AUC). We also assessed drug-use impulsivity (subscales from the Impulsive Relapse Questionnaire [IRQ]) and estimated intelligence (Shipley IQ) as predictors of DD. Heroin discounting was greater (smaller AUC) during withdrawal than satiation. In regression analyses, lower intelligence and IRQ Capacity for Delay as well as higher IRQ Speed (to return to drug use) predicted greater heroin discounting in the satiation condition. Lower intelligence and higher IRQ Speed predicted greater discounting in the withdrawal condition. Sex, race, substance use variables, and other IRQ subscales were not significantly related to the withdrawal or satiation DD behavior. In summary, heroin discounting was temporally rapid, pharmacologically state dependent, and predicted by drug-use impulsivity and estimated intelligence. These findings highlight a novel and sensitive measure of acute DD that is easy to administer.

Contributions to drug abuse research of Steven R. Goldberg's behavioral analysis of stimulus-stimulus contingencies.

By the mid-1960s, the concept that drugs can function as reinforcing stimuli through response-reinforcer contingencies had created a paradigm shift in drug abuse science. Steve Goldberg's first several publications focused instead on stimulus-stimulus contingencies (respondent conditioning) in examining Abraham Wikler's two-factor hypothesis of relapse involving conditioned withdrawal and reinforcing effects of drugs. Goldberg provided a compelling demonstration that histories of contingencies among stimuli could produce lasting withdrawal reactions in primates formerly dependent on opioids. Other studies conducted by Goldberg extended the analysis of effects of stimulus-stimulus contingencies on behavior maintained by opioid reinforcing effects and showed that withdrawal-inducing antagonist administration can produce conditioned increases in self-administration. Subsequent studies of the effects of stimuli associated with cocaine injection under second-order schedules showed that the maintenance of behavior with drug injections was in most important aspects similar to the maintenance of behavior with more conventional reinforcers when the behavior-disrupting pharmacological effects of the drugs were minimized. Studies on second-order schedules demonstrated a wide array of conditions under which behavior could be maintained by drug injection and further influenced by stimulus-stimulus contingencies. These schedules present opportunities to produce in the laboratory complex situations involving response- and stimulus-stimulus contingencies, which go beyond simplistic pairings of stimuli and more closely approximate those found with human drug abusers. A focus on the response- and stimulus-stimulus contingencies, and resulting quantifiable changes in objective and quantifiable behavioral endpoints exemplified by the studies by Steve Goldberg, remains the most promising way forward for studying problems of drug dependence.

Validation of a Simple Thyroid Cancer Dosimetry Model Based on the Fractional Whole-Body Retention at 48 Hours Post-Administration of (131)I.

Standard dosimetric methods to determine the maximum tolerated activity (MTA) of (131)I for the treatment of metastatic, well-differentiated thyroid cancer (DTC) are time-consuming and require complex analysis. As a result, reliable, accurate, and simplified methods are desirable. The objective of this study was to evaluate the validity of a simple regression dosimetry model. Previously, the authors reported a bi-exponential model for estimating the MTA of (131)I for the treatment of metastatic DTC based on a limit of 2 Gy to the blood. This model uses the patient's body surface area (BSA) along with the fractional whole-body retention (WBR) at 48 hours following oral administration of a diagnostic dosage of (131)I. A bi-exponential regression model was developed between the MTA normalized to the patient's BSA and the percent retention value at the 48-hour time point (R): MTA (GBq)/BSA (m(2)) = (13.91 · e(-0.0387R) + 42.33 · e(-0.8522R)). In this study, the same model was applied to a different set of adult patients referred for dosimetry and possible (131)I treatment of DTC under conditions of thyroid hormone withdrawal or recombinant human thyrotropin (rhTSH) stimulation. All patients (n = 170; 96 female) referred to the authors' clinic for dosimetry and possible (131)I treatment for metastatic DTC during the collection period were included in this study, apart from those undergoing renal dialysis. The MTA predicted (MTAp) using the model described above was compared to the measured MTA (MTAm), with statistical analysis performed using ProStat v4.5. In this group, the MTAm ranged from 2.3 to 41.1 GBq. The linear correlation between the MTAp and MTAm was excellent (r = 0.96), with an average deviation of only ± 1.2%. However, to avoid overdosing a patient on the basis of the MTAp, a weighting factor (<1.0) should be applied (e.g., using a value of 0.7 would result in only one patient receiving a prescribed activity of (131)I that exceeded the MTAm [<3%]). The % 48-hour WBR as determined by the bi-exponential function noted herein with reasonable restrictions has been validated as a reliable simplified dosimetry model.

The goldfish conditioned withdrawal preparation: effects of some basic methodological variables.

Barela (Psychological Reports, 110: 173-186, 2012) presented a novel preparation for the experimental study of classical fear conditioning in goldfish, and successfully employed it in the demonstration of several basic conditioning principles. The present research addressed some basic methodological questions using a modified version of this preparation. Results indicated that the modification made to the visual CS increased its efficacy, and that conditioning to this stimulus was directly related to the number of CS-US trials given, US intensity, and intertrial interval. In addition, conditioning was detected with interstimulus intervals both shorter and longer than those used previously, as well as with an auditory CS. Methodological implications for the future employment of this preparation are discussed.

Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice

Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, which suggests that the developing hippocampus may be sensitive to the effects of caffeine.

Visco-elasto-plastic compaction of aquitards due to groundwater withdrawal in Shanghai, China

Long-term excessive groundwater withdrawal can cause aquifer systems to compact, and land subsidence ensues. The compaction of aquitards lags behind the change of groundwater level in adjacent aquifers, which is attributed to low hydraulic conductivity and great creep deformation of aquitards. Under the condition of groundwater withdrawal, aquitard clays may compact visco-elastically, elasto-plastically or visco-elasto-plastically, depending on the effective stress history they have experienced. Laboratory data manifest that aquitard clays have a similar constitutive relationship to aquifer sands, therefore the double-yielding visco-elasto-plastic mechanical model proposed for aquifer sands is applicable to aquitard clays. A fully coupled one-dimensional visco-elasto-plastic compaction model is constructed for aquitards to predict their compaction by integrating the double-yielding mechanical model with the flow governing equation of groundwater. The comprehensive compaction model not only makes the groundwater flow and soil deformation coupled, but also takes into account the complex deformation characteristics of aquitard units under long-term groundwater withdrawal, such as creep and plastic deformation under reloading.

Unilateral hand contractions produce motivational biases in social economic decision making.

Unilateral hand contractions have been shown to induce relative activation of the contralateral hemisphere, which is in turn associated with distinct motivational states. Specifically, right hand contraction increases relative left activation and promotes an approach state, and left hand contractions promote relative right activation and withdrawal states. Using the same hand clenching technique, the present study extends this research to examine the incidental role of motivational tendency on interactive economic decision making. A total of 75 right-handed participants were randomly assigned to 1 of 3 conditions, including withdrawal/left-hand contractions, approach/right-hand contractions, and control/no contraction. Participants completed 2 well-known economic tasks, namely the Ultimatum Game (UG), Dictator Game (DG). In the UG, we found that relative to individuals in the withdrawal condition, those in the approach (right-hand contraction) condition made higher monetary offers to human partners who could either accept or reject these offers. Moreover, those in the approach condition rejected significantly more unfair offers from human partners. This study provides the first evidence that hemispheric activation, using unilateral muscle contractions, may play a causal role in biasing social economic decision making. Overall, there results suggest that greater relative left frontal activation promotes reward-maximizing strategies, consistent with an approach motivation, and relative right frontal activation may decrease such strategic tendencies.

Delay and probability discounting: Examining the relationship between caffeine withdrawal and impulsivity

Event Abstract Back to Event Delay and probability discounting: Examining the relationship between caffeine withdrawal and impulsivity Glen Tanner1* and Stephen Provost1 1 Southern Cross University, Psychology, School of Health and Human Sciences, Australia Impulsivity is linked to drug dependency. Research has found that both nicotine and amphetamine-dependent individuals delay discount (DD) hypothetical monetary gains more steeply than matched controls. Within these dependent populations, discounting levels have been shown to spike during cessation/withdrawal, providing insight to perhaps why certain individuals respond better to abstinence-based treatments than others. Despite being the world's most widely consumed psychostimulant, the effect between caffeine withdrawal and impulsivity is yet to be examined using the delay discounting measure. Aims: The present study aims to explore the relationship between caffeine withdrawal and impulsivity as measured by the delay discounting (DD) procedure. It was predicted that abstinent regular coffee/caffeine consumers would show steeper levels of discounting than non-abstinent coffee/caffeine consumers. Method: Participants were randomly allocated to either a before or after caffeine consumption group. Both groups completed identical online surveys regarding their regular caffeine consumption, followed by two hypothetical discounting tasks. Discounting tasks involved hypothetical questions regarding investment choices. Results on discounting tasks were calculated via the ‘area under the curve’ (AUC) method. Results: The caffeine withdrawal condition was predicted to have steeper discounting curves than the non-caffeine condition. A positive correlation was predicted between the level of weekly caffeine consumption and discounting levels. Conclusions: Validating previous research for other stimulants, conditional support was found for a correlation between caffeine withdrawal and impulsivity. However, these results could also be explained by other well-documented symptoms of stimulant withdrawal such as confusion or anxiety. Further efforts should be devoted to determining the effect anxiety has on impulsivity as measured by the delay discounting procedure. Keywords: Caffeine, impulsivity, withdrawal, delay discounting, dependency Conference: 12th Annual Psychology Research Conference, 2015, Coffs Harbour, Australia, 25 Sep - 26 Sep, 2015. Presentation Type: Research Topic: Psychology Citation: Tanner G and Provost S (2015). Delay and probability discounting: Examining the relationship between caffeine withdrawal and impulsivity. Front. Psychol. Conference Abstract: 12th Annual Psychology Research Conference, 2015. doi: 10.3389/conf.fpsyg.2015.66.00003 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Sep 2015; Published Online: 23 Sep 2015. * Correspondence: Mr. Glen Tanner, Southern Cross University, Psychology, School of Health and Human Sciences, Coffs Harbour, NSW, 2450, Australia, g.tanner.10@student.scu.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Glen Tanner Stephen Provost Google Glen Tanner Stephen Provost Google Scholar Glen Tanner Stephen Provost PubMed Glen Tanner Stephen Provost Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Alcohol Withdrawal and Cerebellar Mitochondria.

Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new therapy to manage cerebellar disorders associated with hyperexcitatory CNS disorders like ethanol withdrawal.

Effects of chronic mild stress on the development of drug dependence in rats.

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes.

The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of the transcriptomic response of this pathway to variations in nutrient availability.

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Neuroimaging studies of chronic smokers report altered activity of several neural regions involved in the processing of rewarding outcomes. Neuroanatomical evidence suggests that these regions are directly connected to the tongue muscle through the corticobulbar pathways. Accordingly, we examined whether corticobulbar excitability might be considered a somatic marker for nicotine craving. We compared motor-evoked potential (MEP) amplitudes recorded from the tongue and the extensor carpi radialis (control muscle) of chronic smokers under drug withdrawal and intake conditions as well as a nonsmoker group. All participants were tested during passive exposure to pictures showing a smoking cue or a meaningless stimulus. In the intake condition, chronic smokers were asked to smoke a real cigarette (CSn: group 1) or a placebo (CSp: group 2). Results show that MEP amplitudes recorded from the tongues of participants in the CSn and CSp groups under the withdrawal condition were selectively enhanced during exposure to a smoking cue. However, this effect on tongue MEP amplitudes disappeared in the intake condition for both the CSn and CSp groups. Limitations include the fact that the study was conducted in 2 different laboratories, the small sample size, the absence of data on chronic smoker craving strength and the different tastes of the real and placebo cigarettes. These results suggest that, in chronic smokers, tongue muscle MEP amplitudes are sensitive to neural processes active under the physiological status of nicotine craving. This finding implicates a possible functional link between neural excitability of the corticobulbar pathway and the reward system in chronic smokers.