Acute Abstinence Research Articles

The interactive effect of anxiety sensitivity and negative smoking cessation cognitions on reductions in cigarette consumption during acute cessation

IntroductionAnxiety sensitivity (AS) as well as negative cognitions about one’s ability to quit smoking represent cognitive-affective vulnerabilities implicated in smoking cessation success. However, the extent to which one’s perceived sensitivity to anxiety and cessation-related cognitions uniquely and interactively affect acute abstinence outcomes has not been examined. The current study examined the interactive effects of AS and cessation cognitions on percent reductions in cigarettes smoked during the first 24-h of a quit attempt. MethodsAdult cessation-motivated smokers (n = 64; Mage = 34.21, SD = 11.49) completed a planned quit attempt. AS and cessation cognitions were evaluated prior to quit day. Percent cigarette reduction was assessed by number of cigarettes smoked the day before and during the first 24 h of the quit attempt. ResultsSignificant interactive effects between AS and cessation cognitions (i.e., expectation of success in quitting, intolerance of withdrawal symptoms, and lack of cognitive coping) were observed. Consistent with hypotheses, individuals reporting higher AS and a greater perceived ability to tolerate withdrawal as well as a greater expectation of success reported larger reductions in cigarettes post quit compared to those who did not endorse these beliefs. Unexpectedly, individuals reporting lower AS who did not endorse the belief that they should be able to tolerate withdrawal discomfort, or a lack of cognitive coping, reported larger reductions compared to those who did endorse this belief. ConclusionAS may interact with specific cessation cognitions. Pre-cessation beliefs that individuals will be successful and be able to tolerate withdrawal symptoms may support cessation efforts.

Investigating tobacco withdrawal in response to reduced nicotine cigarettes among smokers with opioid use disorder and other vulnerabilities.

Individuals with opioid use disorder (OUD) have high prevalence of smoking and poor cessation outcomes. Data suggest that smokers with OUD may experience heightened nicotine reinforcement and more severe tobacco withdrawal compared to smokers without OUD. The Food and Drug Administration is currently considering reducing the nicotine content of cigarettes to reduce smoking prevalence and smoking-related disease. It is critical to understand the effects of reduced nicotine content cigarettes (RNCCs) on tobacco withdrawal in this subgroup. In this secondary analysis, we investigated the ability of RNCCs to attenuate acute tobacco withdrawal and craving severity in smokers with OUD versus those without substance use disorders (SUDs). Smokers maintained on methadone or buprenorphine (opioid-maintained [OM]; n = 65) versus without other SUDs (i.e., non-SUD; n = 135) completed 5 laboratory sessions wherein they smoked their usual brand (UB) or a research cigarette varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g of tobacco) under double-blind, acute abstinence conditions. Participants completed the Minnesota Tobacco Withdrawal Scale, including a desire to smoke (craving) item, before and every 15 min for 1 hr following smoking each cigarette. Tobacco withdrawal and craving did not differ significantly by OM status in response to UB or RNCCs. In addition to the Dose × Time interaction, greater depression and cigarette dependence consistently predicted withdrawal and craving (ps < .05). Across all cigarettes, tobacco withdrawal and craving did not significantly differ by OM status, suggesting that smokers receiving opioid agonist treatment may respond favorably to RNCCs. Additional studies with larger and more diverse samples are needed to address this question more definitively. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Time-Varying Functional Connectivity Decreases as a Function of Acute Nicotine Abstinence

BackgroundThe nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS. MethodsTo isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain. ResultsDuring abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms. ConclusionsUsing multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence.

Heightened Exploratory Behavior Following Chronic Excessive Ethanol Drinking: Mediation by Neurotensin Receptor Type 2 in the Anterior Paraventricular Thalamus.

Chronic, excessive alcohol drinkers, even without dependence, can exhibit changes in behavior and neurochemical systems. Identifying these changes and their relationship with one another could provide novel avenues for the prevention and treatment of alcohol use disorder. We recently demonstrated, in rats, that neurotensin (NTS) in the paraventricular thalamus (PVT) regulates excessive ethanol (EtOH) drinking. Here, we investigate the effects of chronic EtOH drinking on the PVT-NTS system and its contribution to EtOH-induced behavioral changes. We gave adult male Long-Evans rats 20% EtOH under the intermittent access 2-bottle-choice paradigm or maintained them on chow and water for up to 11weeks. Prior to EtOH exposure and following several weeks of access, during acute abstinence, we tested these groups for multiple behaviors. In the 12th week, during acute abstinence, we examined gene expression and peptide levels of NTS and its receptors in the anterior and posterior subregions of the PVT. Finally, in chronic EtOH drinkers, during acute abstinence, we microinjected the NTS receptor type 2 (NTS2R) agonist, JMV-431, in the anterior PVT (aPVT) and examined subsequent EtOH intake and behavior. Following chronic intermittent EtOH access, rats were classified by cluster analysis as high or low EtOH drinkers. High EtOH drinkers spent more time in the light chamber of a light-dark box and open arms of an elevated plus maze and entered fewer familiar holes in a hole-board apparatus. These differences were absent prior to EtOH exposure but were detectable as early as 4weeks into drinking. Time in the light chamber following chronic drinking also predicted level of subsequent drinking. High EtOH drinkers also showed elevated protein levels of NTS2R in the aPVT, and pharmacological stimulation of aPVT NTS2R in low drinkers mimicked the increased time spent in the light chamber that was observed in high drinkers. Our findings suggest that chronic, excessive, but not lower level, EtOH drinking induces heightened or flexible exploratory behavior, which predicts future EtOH drinking and is partly mediated by elevated NTS2R signaling in the aPVT. These EtOH-induced alterations represent adaptations that could perpetuate excessive drinking and lead to the development of EtOH dependence.

Management protocol for the naltrexone implant in the patients with acute abstinence symptoms: Mexican case series

Abuse and addiction to opioids, including prescription painkillers, heroin and synthetic opioids such as fentanyl, buprenorphine, constitute a serious crisis that affects public health and has economic repercussions.1 Naltrexone implants are effective tools used in hospital environments and they can not only save patient´s lives but also maintain a prolonged effect, free of relapse and with better therapeutic adherence. The aim of this study is to describe that the management protocol of acute abstinence symptoms in patients with a history of opioid use prior to naltrexone implant placement.

Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not inhibitory control: converging fMRI evidence from Go-Nogo and Flanker tasks.

Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here we examine the effects of nicotine dependence (trait; smokers (n = 24) vs. non-smoking controls; n = 20) and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of inhibitory control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence, and pharmacological manipulation. However, effects were driven entirely by conditions that required less inhibitory control. When demand for inhibitory control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.

The development and validation of a human screening model of tobacco abstinence

IntroductionGiven the low efficacy of smoking cessation methods, an experimental medicine model indicating smoking abstinence would be of great benefit to the development of new treatments. Hence the sensitivity of cognitive tasks and ambulatory craving measures to smoking abstinence were investigated. MethodsCognitive tasks and ambulatory ratings of craving were assessed for sensitivity to acute abstinence (experiment 1), and nicotine replacement therapy administration (NRT) (experiment 2). ResultsIn experiment 1 go/no-go performance was improved (Mean Difference [MD] -0.99, 95% CI: −1.90 to −0.08) and craving was lower (Regression Coefficient [RC] −33.39, 95% CI: -39.96 to -26.82) in satiated compared with abstinent smokers. There was no clear evidence that N-back (MD 0.64, 95% CI: −0.42 to 2.51), delay discounting (MD 0.01, 95% CI: 0.001 to 0.005) or dot probe performance (MD 0.61, 95% CI: −0.87 to 1.54) were sensitive to acute abstinence. In experiment 2 go/no-go performance was improved (MD 1.12, 95% CI: 0.16–2.08) and craving was lower (RC −18.59, 95% CI: −24.63 to −12.55) smokers abstinent overnight receiving NRT compared with placebo. There was no clear evidence that N-back (MD −0.25, 95% CI: −1.45 to 0.94), delay discounting (MD 0.01, 95% CI: -0.002 to 0.004) or dot probe performance (MD −0.49, 95% CI: −1.61 to −0.64) were sensitive to NRT. ConclusionsFindings from two experiments converge to suggest that abstinence in smokers reliably increases ambulatory craving assessments and, to a lesser extent, decreases go/no-go task performance. These findings can be utilized in the development of an experimental medicine model to test novel treatments for smoking cessation.

Distress intolerance and withdrawal severity among daily smokers: The role of smoking abstinence expectancies

BackgroundDistress intolerance (DI), the perceived inability to withstand distress, is implicated in cigarette smoking maintenance. Greater DI may contribute to anticipation of negative outcomes from smoking abstinence, which in turn could contribute to withdrawal symptom severity. The current study aimed to evaluate (1) the association between DI and acute abstinence expectancies and (2) the potential mediating role of abstinence expectancies in the relationship between DI and withdrawal symptom severity. MethodParticipants (n = 444) were daily smokers who reported at least one prior quit attempt, participating in a larger online study on distress and smoking. DI, subjective nicotine withdrawal, and smoking abstinence expectancies were assessed using the Distress Tolerance Scale (DTS), Minnesota Nicotine Withdrawal Scale (MNWS), and Smoking Abstinence Expectancies Questionnaire (SAEQ). ResultsDTS was significantly negatively associated with SAEQ, specifically Negative Mood (r = −0.37, p < .001), Somatic Symptoms (r = −0.47, p < .001), and Harmful Consequences (r = −0.59, p < .001) subscales, but was not associated with Positive Expectancies subscale (r = 0.05, p = .31). Results indicated a significant effect of DTS on withdrawal symptom severity via SAEQ. Follow-up analyses indicated that the indirect effects were driven specifically by SAEQ Negative Mood and Harmful Consequences subscales. DiscussionDI is related to more negative abstinence expectancies, particularly affective aspects of abstinence, which may contribute to the severity of nicotine withdrawal symptoms. This study provides initial evidence of a specific cognitive process that may explain why DI contributes to heightened subjective experience of nicotine withdrawal symptoms.

Cannabis-dependent adolescents show differences in global reward-associated network topology: A functional connectomics approach.

Adolescence may be a period of increased vulnerability to the onset of drug misuse and addiction due to changes in developing brain networks that support cognitive and reward processing. Cannabis is a widely misused illicit drug in adolescence which can lead to dependence and alterations in reward-related neural functioning. Concerns exist that cannabis-related alterations in these reward networks in adolescence may sensitize behaviour towards all forms of reward that increase the risk of further drug use. Taking a functional connectomics approach, we compared an acutely abstinent adolescent cannabis-dependent (CAN) group with adolescent controls (CON) on global measures of network topology associated with anticipation on a monetary incentive delay task. In the presence of overall superior accuracy, the CAN group exhibited superior global connectivity (clustering coefficient, efficiency, characteristic path length) during monetary gain anticipation compared with the CON group. Additional analyses showed that the CAN group exhibited significantly greater connectivity strength during monetary gain anticipation across a subnetwork that included mesocorticolimbic nodes involving both interhemispheric and intrahemispheric connections. We discuss how these differences in reward-associated connectivity may allude to subtle functional alterations in network architecture in adolescent cannabis-dependence that could enhance the motivation for nondrug reward during acute abstinence.

Multi-method assessment of distress tolerance and smoking-related factors among adult daily smokers.

Although distress tolerance (DT) is associated with smoking lapse and relapse outcomes, few studies have conducted a rigorous assessment of DT across domain and method in the context of acute abstinence. In a human laboratory-based study of 106 adult daily smokers, we examined between multiple indices of DT and smoking lapse, withdrawal processes, and motivation to quit. We expected that low DT would be associated with shorter latency to smoke, greater withdrawal severity, and lower motivation to quit. Following a smoking abstinence period (≥ 6 hr deprived), participants completed an assessment battery including both behavioral (mirror-tracing, serial addition, cold pressor, and breath-holding tasks) and self-report measures of DT (general and smoking-specific), withdrawal processes (craving, negative affect, and positive affect), and motivation to quit. Latency to smoke (range = 0-50 min) was assessed in a laboratory analogue task in which delaying smoking was monetarily rewarded. Behavioral and self-report DT indices displayed only modest intercorrelations, indicating different facets of this construct by domain and method of assessment. Tolerance of physical pain was uniquely associated with smoking choice. Both self-report DT measures were associated with abstinence-induced increases in negative affect, while only smoking-specific DT was positively associated with craving. Results are discussed within the context of guiding targeted behavioral interventions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Neural cue reactivity during acute abstinence predicts short-term smoking relapse.

In smokers, neural responses to smoking cues can be sensitive to acute abstinence, but the degree to which abstinence-related cue reactivity contributes to relapse is not fully understood. This study addressed this question in a sample of 75 smokers who were motivated to quit smoking. Participants underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during presentation of visual smoking cues and neutral stimuli on two occasions: once during smoking satiety and once following 24-hour abstinence (order counterbalanced). Following the imaging sessions, participants received brief smoking cessation counseling prior to a short-term (7-day) quit attempt. The primary smoking cessation outcome was biochemically confirmed 7-day relapse. The secondary smoking cessation outcome measure was total number of self-reported days of abstinence. During abstinence (vs satiety), smoking cue reactivity was significantly increased only in the anterior cingulate cortex (ACC); other regions showing a cue (vs neutral) response did not exhibit an abstinence effect in the stringent whole-brain analysis. Participants who showed greater smoking cue reactivity in the ACC during acute abstinence (compared with smoking satiety) were more likely to relapse (OR=2.10 per standard deviation increase in percent signal change [abstinence minus smoking satiety], 95% CI: 1.05 to 4.20, P=0.036). Greater abstinence-induced change in ACC activation also predicted fewer total days abstinent (β=-0.63, 95% CI=0.43 to 0.66, P<0.0001). This study provides the first evidence that changes in smoking cue reactivity in the ACC during acute abstinence predict smoking relapse, thereby improving our understanding of the neurobiology of smoking cessation.

Exploring Sex Differences in the Attenuation of Ethanol Drinking by Naltrexone in Dependent Rats During Early and Protracted Abstinence.

Despite considerable efforts, few drugs are available for the treatment of alcohol (ethanol [EtOH]) use disorder (AUD). EtOH directly or indirectly modulates several aspects of the central nervous system, including neurotransmitter/neuromodulator systems. Relapse vulnerability is a challenge for the treatment of EtOH addiction. EtOH withdrawal symptoms create motivational states that lead to compulsive EtOH drinking and relapse even after long periods of abstinence. Among the therapeutics to treat AUD, naltrexone (NTX) is a pharmacological treatment for relapse. The present study evaluated the effect of NTX on EtOH drinking in male and female EtOH-dependent rats during abstinence. Wistar rats (males and females) were first trained to orally self-administer 10% EtOH. Half of the rats were then made dependent by chronic intermittent EtOH (CIE) vapor exposure, and the other half were exposed to air. Using this model, rats exhibit somatic and motivational signs of withdrawal. At the end of EtOH vapor (or air) exposure, the rats were tested for the effects of NTX (10mg/kg, oral) on EtOH self-administration at 3 abstinence time points: acute abstinence (A-Abst, 8hours), late abstinence (L-Abst, 2weeks), and protracted abstinence (P-Abst, 6weeks). NTX decreased EtOH intake in nondependent rats, regardless of sex and abstinence time point. In postdependent rats, NTX decreased EtOH intake only at a delayed abstinence time point (P-Abst) in males, whereas it similarly reduced EtOH drinking in females at all abstinence time points. The therapeutic efficacy of NTX depends on the time of intervention during abstinence and is different between males and females. The data further suggest that EtOH dependence causes different neuroadaptations in male and female rats, reflected by differential effects of NTX. The results underscore the significance of considering the duration of EtOH abstinence and sex as a biological variable as important factors when developing pharmacotherapies for AUD.

Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice.

Medications that target the noradrenergic system are important therapeutics for depression and anxiety disorders. More recently, clinical studies have shown that the α2-noradrenergic receptor (α2AR) agonist guanfacine can decrease stress-induced smoking relapse during acute abstinence, suggesting that targeting the noradrenergic system may aid in smoking cessation through effects on stress pathways in the brain. Acetylcholine (ACh), like the nicotine in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) to regulate behaviors related to anxiety and depression. We therefore investigated interactions between guanfacine and ACh signaling in tests of anxiolytic and antidepressant efficacy in female and male C57BL/6J mice, focusing on the amygdala as a potential site of noradrenergic/cholinergic interaction. The antidepressant-like effects of guanfacine were blocked by shRNA-mediated knockdown of α2AR in amygdala. Knockdown of the high-affinity β2 nAChR subunit in amygdala also prevented antidepressant-like effects of guanfacine, suggesting that these behavioral effects require ACh signaling through β2-containing nAChRs in this brain area. Ablation of NE terminals prevented the anxiolytic- and antidepressant-like effects of the nicotinic partial agonist cytisine, whereas administration of the cholinesterase antagonist physostigmine induced a depression-like phenotype that was not altered by knocking down α2AR in the amygdala. These studies suggest that ACh and NE have opposing actions on behaviors related to anxiety and depression and that cholinergic signaling through β2-containing nAChRs and noradrenergic signaling through α2a receptors in neurons of the amygdala are critical for regulation of these behaviors.

Effect of brief exercise on urges to smoke in men and women smokers

IntroductionAlthough smoking urges have been demonstrated to vary by gender and also be influenced by exercise, it is unknown if exercise has a differential effect on smoking urges by gender. This study aimed to explore gender-specific effects of an acute bout of exercise on cessation-related symptoms in men and women smokers during acute abstinence. MethodsWe enrolled smokers (≥5 cigarettes/day) who were 18–40years old for a study on exercise and smoking behavior. Participants abstained from smoking for at least 3h, prior to measurement of their maximal oxygen consumption tested, which was the acute bout of exercise. Prior to and after the exercise, participants completed the Questionnaire of Smoking Urges – Brief and the Minnesota Nicotine Withdrawal Scale. ResultsParticipants (n=38; 61% women) were, on average, 30.0±0.9years old and smoked 13.0±0.8 cigarettes/day. All measured aspects of cessation-related symptoms significantly improved after the exercise in both men and women. In women there was a significant decline in anticipated relief from negative affect after the exercise (women: −0.45±0.20, p=0.0322; men: −0.41±0.26, p=0.1312). In men there was a significant decline in the intention to smoke after the exercise (men: −0.77±0.23, p=0.0053; women: −0.66±0.37, p=0.0909). ConclusionsAn acute bout of exercise reduced smoking urges in both men and women smokers during an acute state of abstinence. Additional research is needed to replicate these observations in a larger, more diverse sample, and to explore the implication of these observations on cessation.

Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats

Chronic intermittent exposure to ethanol (EtOH; CIE) that produces binge-like levels of intoxication has been associated with age-dependent deficits in cognitive functioning. Male Sprague–Dawley rats were exposed to CIE (5g/kg, 25% EtOH, 13 intragastric gavages) beginning at three ages: early adolescence (postnatal day [PD] 28), mid-adolescence (PD35) and adulthood (PD72). In experiment 1, rats were behaviorally tested following CIE. Spatial memory was not affected by CIE, but adult CIE rats were impaired at acquiring a non-spatial discrimination task and subsequent reversal tasks. Rats exposed to CIE during early or mid-adolescence were impaired on the first reversal, demonstrating transient impairment in behavioral flexibility. Blood EtOH concentrations negatively correlated with performance on reversal tasks. Experiment 2 examined changes in brain-derived neurotrophic factor (BDNF) levels within the frontal cortex (FC) and hippocampus (HPC) at four time points: during intoxication, 24 h after the final EtOH exposure (acute abstinence), 3 weeks following abstinence (recovery) and after behavioral testing. HPC BDNF levels were not affected by CIE at any time point. During intoxication, BDNF was suppressed in the FC, regardless of the age of exposure. However, during acute abstinence, reduced FC BDNF levels persisted in early adolescent CIE rats, whereas adult CIE rats displayed an increase in BDNF levels. Following recovery, neurotrophin levels in all CIE rats recovered. Our results indicate that intermittent binge-like EtOH exposure leads to acute disruptions in FC BDNF levels and long-lasting behavioral deficits. However, the type of cognitive impairment and its duration differ depending on the age of exposure.

Assessment of pain in adolescents: Influence of gender, smoking status and tobacco abstinence

PurposeWe examined sex differences between smokers and nonsmokers in pain threshold, tolerance, and intensity and the effect of pain on cardiovascular measures, withdrawal, and craving during acute smoking abstinence. MethodsNinety-six (53 smokers, 43 nonsmokers) adolescents completed the Cold Pressor Task (CPT) to assess pain responses after minimal (1h) and 42-hour smoking deprivation. Vital signs and craving were assessed before and after CPT completion. ResultsSmokers, compared to nonsmokers, had significantly lower pain tolerance (p<0.01) and pain threshold (p<0.001). Female smokers had significantly lower pain tolerance prior to, and following, 42-hour deprivation compared to male smokers (p's<0.01), male nonsmokers (p's<0.01), and female nonsmokers (p's<0.001), while male smokers demonstrated significantly decreased pain tolerance following 42-hour deprivation (p<0.05). Additionally, during minimal deprivation, at time of hand removal, female smokers had higher pain intensity compared to female nonsmokers (p<0.05) and male smokers (p<0.01). Withdrawal was not significantly correlated with any CPT measures or subjective pain during or following minimal deprivation or acute abstinence. Craving was associated with pain 15s after hand submersion (p=0.007) at 42-hour deprivation. ConclusionsSmokers had a lower pain threshold than non-smokers, with female smokers demonstrating lower pain tolerance during minimal deprivation than all comparison groups, and, continuing to have diminished pain tolerance compared to female nonsmokers following 42h of abstinence. Male smokers demonstrated tobacco-deprivation-induced reductions in pain tolerance. Further study of pain-related factors that may contribute to relapse and maintenance of smoking behaviors, and mechanisms of these relationships among adolescent smokers is warranted.

Behavioural tasks sensitive to acute abstinence and predictive of smoking cessation success: a systematic review and meta-analysis.

Background and aimsPerformance on cognitive tasks may be sensitive to acute smoking abstinence and may also predict whether quit attempts fail. Our aim was to conduct a systematic review and meta‐analysis to identify cognitive tasks sensitive to acute abstinence and predictive of smoking cessation success.MethodsEmbase, Medline, PsycInfo and Web of Science were searched up to March 2016. Studies were included if they enrolled adults and assessed smoking using a quantitative measure. Studies were combined in a random effects meta‐analysis.ResultsWe included 42 acute abstinence studies and 13 cessation studies. There was evidence for an effect of abstinence on delay discounting [d = 0.26, 95% confidence interval (CI) = 0.07–0.45, P = 0.005], response inhibition (d = 0.48, 95% CI = 0.26–0.70, P < 0.001), mental arithmetic (d = 0.38, 95% CI = 0.06–0.70, P = 0.018), and recognition memory (d = 0.46, 95% CI = 0.23–0.70, P < 0.001). In contrast, performance on the Stroop (d = 0 .17, 95% CI = −0.17–0.51, P = 0.333) and smoking Stroop (d = 0.03, 95% CI = −0.11–0.17, P = 0.675) task was not influenced by abstinence. We found only weak evidence for an effect of acute abstinence on dot probe task performance (d = 0.15, 95% CI = −0.01–0.32, P = 0.072). The design of the cessation studies was too heterogeneous to permit meta‐analysis.ConclusionsCompared with satiated smokers, acutely abstinent smokers display higher delay discounting, lower response inhibition, impaired arithmetic and recognition memory performance. However, reaction‐time measures of cognitive bias appear to be unaffected by acute tobacco abstinence. Conclusions about cognitive tasks that predict smoking cessation success were limited by methodological inconsistencies.

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator.This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation.For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence.In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction.

Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure.

Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and beta-nerve growth factor (β-NGF) in the prefrontal cortex and hippocampus were also assessed at different time-points: during CET, following acute abstinence (48-hrs), and after protracted abstinence (6–8 wks). Our results revealed that an adolescent onset of CET leads to increased EtOH consumption that persisted into adulthood. In both adult and adolescent onset CET groups, there were significant long-term reductions in prefrontal cortical mBDNF and β-NGF levels. However, only adult onset CET rats displayed decreased hippocampal BDNF levels. Spatial memory, assessed by spontaneous alternation and delayed alternation, was not significantly affected by CET as a function of age of drinking onset, but higher blood–EtOH levels were correlated with lower spontaneous alternation scores. Regardless of the age of onset, EtOH exposed rats were impaired on non-spatial discrimination learning and displayed inflexible behavioral patterns upon reversal learning. Our results indicate that adolescent EtOH exposure changes long-term consumption patterns producing behavioral and neural dysfunctions that persist across the lifespan.

Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction.