Motivational Properties Research Articles

Decrease of cocaine, but not heroin, self-administration and relapse by the tyrosine kinase inhibitor masitinib in male Sprague Dawley rats

RationaleAccumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties. Masitinib, a novel tyrosine kinase inhibitor with high selectivity for c-Kit, Fyn and Lyn, may alter the aberrant consequences of the activation of these tyrosine kinases by cocaine and heroin.ObjectiveWe investigated in rats the effect of a chronic oral treatment with masitinib (20 mg/kg) on the reinforcing and motivational properties of self-administered cocaine (250 μg/infusion) and heroin (40 μg/infusion).MethodsThree different cohorts of rats were trained instrumentally to respond for cocaine, heroin or food under continuous reinforcement. In each group, we assessed the influence of chronic daily treatment with masitinib on the maintenance of instrumental responding and intake and the motivation for the reinforcer. Thus, masitinib and vehicle-treated rats were challenged to adapt to high behavioural demand, to respond under a progressive ratio schedule of reinforcement and to reinstate instrumental responding after extinction and/or abstinence.ResultsMasitinib selectively decreased cocaine intake, the motivation for cocaine and the subsequent propensity to respond for cocaine under extinction, while having no effect on instrumental responding for heroin or food.ConclusionThe present findings suggest masitinib, a drug with proven efficacy in CNS disorders, could represent a novel treatment for cocaine addiction provided its influence on the reinforcing and incentive properties of the drug is confirmed.

Nicotine affects ethanol-conditioned taste, but not place, aversion in a simultaneous conditioning procedure.

The conditioned taste aversion (CTA) induced by ethanol is a key factor limiting ethanol intake. Nicotine, a drug co-consumed with ethanol, may decrease this aversion by modulating the unconditioned effects of ethanol or by disrupting the association between ethanol and its associated cues. This study analyzed ethanol-induced CTA and conditioned place aversion (CPA) in Long-Evans rats with subchronic exposure to nicotine. The rats were treated with nicotine (0.0 or 0.4mg/kg) three times before conditioning (on lickometer training sessions 3, 4, and 5) and across conditioning days. During the conditioning the rats were given ethanol (1.3g/kg) preceded and followed by presentation of a taste (NaCl) and tactile (rod or hole floors) conditioned stimulus (CS+), respectively. On CS- conditioning days, the rats were given vehicle and exposed to alternative stimuli. Three CTA and CPA testing sessions were then conducted. It was found that nicotine reduced ethanol-induced CTA and enhanced locomotor activity, but did not significantly modify the magnitude of ethanol-induced CPA. The effects of nicotine on CTA were observed during both conditioning and testing sessions, and were specific to the NaCl CS+, having no effect on reactivity to water. The dissociation between the effect of nicotine on ethanol-induced CTA and CPA suggests that nicotine does not alter ethanol's motivational properties by generally increasing its positive rewarding effects, nor does it blunt all aversive-like responses to this drug. Instead, nicotine may impede ethanol-induced CTA induced by ethanol by disrupting the neural underpinnings of this specific form of associative learning.

Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine’s reinforcing properties is controlled by the GABAB receptor.

Motivational sensitivity of outcome-response priming: Experimental research and theoretical models

Outcome-response (O-R) priming is at the core of various associative theories of human intentional action. This is a simple and parsimonious mechanism by which activation of outcome representations (e.g. thinking about the light coming on) leads to activation of the associated motor patterns required to achieve it (e.g. pushing the light switch). In the current manuscript, we review the evidence for such O-R associative links demonstrated by converging (yet until now, separate) strands of research. While there is a wealth of evidence that both the perceptual and motivational properties of an outcome can be encoded in the O-R association and mediate O-R priming, we critically examine the integration of these mechanisms and the conditions under which motivational factors constrain the sensory O-R priming effect. We discuss the clinical relevance of this O-R priming mechanism, whether it can satisfactorily account for human goal-directed behaviour, and the implications for theories of human action control.

Nicotine-enhanced Pavlovian conditioned approach is resistant to omission of expected outcome

Conditioned stimuli contribute to the resilience of nicotine addiction in that nicotine-associated cues can influence smokers and promote relapse. These stimuli are thought to acquire incentive motivational properties through a Pavlovian mechanism, and this phenomenon can be measured in animals by observing conditioned approach to the conditioned stimulus (sign-tracking) or to the location of unconditioned stimulus delivery (goal-tracking). Goal-tracking is thought to be more flexible than sign-tracking in response to changes in expected outcome. Nicotine exposure can increase the expression of conditioned responses, and we hypothesized that animals exposed to nicotine would also exhibit less flexible conditioned responses after a change in the expected unconditioned stimulus. Adult male rats were exposed to nicotine (0.4mg/kg, s.c.) or saline before Pavlovian conditioned approach training sessions. After training, animals underwent test sessions that reduced (water substitution) or withheld (omission) the unconditioned stimulus (US, 20% sucrose). As expected, nicotine enhanced sign- and goal-tracking. Water substitution moderately and nonspecifically reduced both sign- and goal-tracking in all rats. In contrast, US omission only reduced goal-tracking, with robust effects in saline-exposed rats and smaller effects in nicotine-exposed rats. These data support the hypothesis that both sign-tracking and nicotine exposure confer behavioral inflexibility under US omission.

Working for beverages without being thirsty: Human Pavlovian-instrumental transfer despite outcome devaluation

The incentive-motivational salience acquired by a Pavlovian conditioned stimulus (CS) is reflected by its ability to strengthen the performance of a separately learned instrumental action exerted to obtain an outcome, a phenomenon known as Pavlovian-Instrumental transfer (PIT). By means of a PIT paradigm, the present study addressed whether the CS motivational properties vary dynamically with the value of the associated outcome. Previous studies on human PIT and outcome devaluation have provided mixed results, showing that in some cases post-training devaluation leaves PIT unaffected when outcomes are palatable foods or drugs, and when the devalued outcome is not consumed immediately. In Experiment 1, thirsty participants first learned to squeeze a rubber bulb to accumulate a beverage (plain water or sugary drink); then participants learned Pavlovian associations between cues and the beverage. When tested in extinction, a PIT effect emerged as expected. In Experiment 2, the PIT effect emerged even despite participants quenched their thirst before the test phase. Our results suggest that the incentive properties of a CS can surprisingly and irrationally endure the devaluation of the associated outcome even when plain water is used as reward, and thirst is quenched by immediate reward consumption. This result may provide important insights in the understanding of the psychological mechanisms underlying different types of addiction.

Adding immersive virtual reality to a science lab simulation causes more presence but less learning

Virtual reality (VR) is predicted to create a paradigm shift in education and training, but there is little empirical evidence of its educational value. The main objectives of this study were to determine the consequences of adding immersive VR to virtual learning simulations, and to investigate whether the principles of multimedia learning generalize to immersive VR. Furthermore, electroencephalogram (EEG) was used to obtain a direct measure of cognitive processing during learning. A sample of 52 university students participated in a 2 × 2 experimental cross-panel design wherein students learned from a science simulation via a desktop display (PC) or a head-mounted display (VR); and the simulations contained on-screen text or on-screen text with narration. Across both text versions, students reported being more present in the VR condition (d = 1.30); but they learned less (d = 0.80), and had significantly higher cognitive load based on the EEG measure (d = 0.59). In spite of its motivating properties (as reflected in presence ratings), learning science in VR may overload and distract the learner (as reflected in EEG measures of cognitive load), resulting in less opportunity to build learning outcomes (as reflected in poorer learning outcome test performance).

Retrograde inhibition by a specific subset of interpeduncular α5 nicotinic neurons regulates nicotine preference

Repeated exposure to drugs of abuse can produce adaptive changes that lead to the establishment of dependence. It has been shown that allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) gene CHRNA5 is associated with higher risk of tobacco dependence. In the brain, α5-containing nAChRs are expressed at very high levels in the interpeduncular nucleus (IPN). Here we identified two nonoverlapping α5 + cell populations (α5- Amigo1 and α5- Epyc ) in mouse IPN that respond differentially to nicotine. Chronic nicotine treatment altered the translational profile of more than 1,000 genes in α5- Amigo1 neurons, including neuronal nitric oxide synthase (Nos1) and somatostatin (Sst). In contrast, expression of few genes was altered in the α5- Epyc population. We show that both nitric oxide and SST suppress optically evoked neurotransmitter release from the terminals of habenular (Hb) neurons in IPN. Moreover, in vivo silencing of neurotransmitter release from the α5- Amigo1 but not from the α5- Epyc population eliminates nicotine reward, measured using place preference. This loss of nicotine reward was mimicked by shRNA-mediated knockdown of Nos1 in the IPN. These findings reveal a proaddiction adaptive response to chronic nicotine in which nitric oxide and SST are released by a specific α5+ neuronal population to provide retrograde inhibition of the Hb-IPN circuit and thereby enhance the motivational properties of nicotine.

'Hot' vs. 'cold' behavioural-cognitive styles: motivational-dopaminergic vs. cognitive-cholinergic processing of a Pavlovian cocaine cue in sign- and goal-tracking rats.

Discrete Pavlovian reward cues acquire more potent incentive motivational properties (incentive salience) in some animals (sign-trackers; STs) compared to others (goal-trackers; GTs). Conversely, GTs appear to be better than STs in processing more complex contextual cues, perhaps reflecting their relatively greater bias for goal-directed cue processing. Here, we investigated the activity of two major prefrontal neuromodulatory input systems, dopamine (DA) and acetylcholine (ACh), in response to a discrete Pavlovian cue that was previously paired with cocaine administration in STs and GTs. Rats underwent Pavlovian training in which light cue presentations were either paired or unpaired with an intravenous cocaine infusion. Following a 10-day abstinence period, prefrontal dialysates were collected in STs and GTs during cue presentations in the absence of cocaine. In STs, the cue previously paired with cocaine significantly increased prefrontal DA levels. DA levels remained elevated over baseline across multiple cue presentation blocks, and DA levels and approaches to the cue were significantly correlated. In STs, ACh levels were unaffected by cue presentations. In contrast, in GTs, presentations of the cocaine cue increased prefrontal ACh, but not DA, levels. GTs oriented towards the cue at rates similar to STs, but they did not approach it and elevated ACh levels did not correlate with conditioned orientation. The results indicate a double dissociation between the role of prefrontal DA and ACh in STs and GTs, and suggest that these phenotypes will be useful for studying the role of neuromodulator systems in mediating opponent behavioural-cognitive styles.

Motivational Objects in Natural Scenes (MONS): A Database of >800 Objects.

In daily life, we are surrounded by objects with pre-existing motivational associations. However, these are rarely controlled for in experiments with natural stimuli. Research on natural stimuli would therefore benefit from stimuli with well-defined motivational properties; in turn, such stimuli also open new paths in research on motivation. Here we introduce a database of Motivational Objects in Natural Scenes (MONS). The database consists of 107 scenes. Each scene contains 2 to 7 objects placed at approximately equal distance from the scene center. Each scene was photographed creating 3 versions, with one object (“critical object”) being replaced to vary the overall motivational value of the scene (appetitive, aversive, and neutral), while maintaining high visual similarity between the three versions. Ratings on motivation, valence, arousal and recognizability were obtained using internet-based questionnaires. Since the main objective was to provide stimuli of well-defined motivational value, three motivation scales were used: (1) Desire to own the object; (2) Approach/Avoid; (3) Desire to interact with the object. Three sets of ratings were obtained in independent sets of observers: for all 805 objects presented on a neutral background, for 321 critical objects presented in their scene context, and for the entire scenes. On the basis of the motivational ratings, objects were subdivided into aversive, neutral, and appetitive categories. The MONS database will provide a standardized basis for future studies on motivational value under realistic conditions.

Stereoselective Differences between the Reinforcing and Motivational Effects of Cathinone-Derived 4-Methylmethcathinone (Mephedrone) In Self-Administering Rats.

Mephedrone (4-methylmethcathinone (4-MMC)) (MEPH) is a new psychoactive substance (NPS) of the synthetic cathinone class. MEPH has a chiral center and exists as two enantiomers (R-,S-MEPH), yet stereospecific effects of MEPH have not been extensively investigated in preclinical assays. Because significant behavioral and neurochemical differences can exist between enantiomers, probing effects of stereochemistry on biological activity enables separation of adverse and therapeutic effects. Our prior work showed that R-MEPH, relative to S-MEPH, produced greater locomotor activation, place preference, and facilitation of brain reward thresholds in rodents. The present study sought to determine if MEPH enantiomers display stereospecific reward and reinforcement in rat self-administration assays. In Experiment 1, rats were trained to self-administer racemic MEPH (0.50 mg/kg/inf), and dose substitution effects of R-MEPH (0.50 mg/kg/inf) and S-MEPH (0.25, 0.50, 2.00 mg/kg/inf) were examined. In Experiment 2, separate rats were trained to self-administer R-MEPH (0.25, 0.50, 2.00 mg/kg/inf) or S-MEPH (0.25, 0.50, 2.00 mg/kg/inf) and were thereafter evaluated under progressive-ratio access conditions. Within this cohort, 50 kHz ultrasonic vocalizations (USVs) were recorded to measure potential differences in subjective positive affect associated with MEPH enantiomer self-administration. We identified enantiomer- and dose-dependent effects on infusions earned during self-administration following acquisition of racemic MEPH, with greatest infusions under low-effort, fixed-ratio 1 access conditions from low-dose S-MEPH self-administration. When taxed with progressive-ratio access conditions, rats trained to self-administer R-MEPH showed higher break points than those of rats trained to self-administer S-MEPH. Additionally, R-MEPH elicited greatest rates of 50 kHz USVs compared to S-MEPH. Taken together, these data suggest that the R-enantiomer of MEPH is primarily responsible for the rewarding, reinforcing, and motivational properties of racemic MEPH, which increases our understanding of stereospecific preferences pertaining to MEPH abuse.

Do current and former cigarette smokers have an attentional bias for e-cigarette cues?

The similarity of e-cigarettes to tobacco cigarettes with regard to shape and usage raises the question of whether e-cigarette cues have the same incentive motivational properties as tobacco cigarette cues. The objective of the present study was to examine whether e-cigarette cues capture and hold smokers' and former smokers' attention and whether the attentional focus is associated with subsequent craving for tobacco cigarettes. It was also examined whether device type (cigalike or mod) moderated this relationship. Participants (46 current daily smokers, 38 former smokers, 48 non-smokers) were randomly assigned to a device type condition in which their eye-movements were assessed while completing a visual probe task. Craving was assessed before and after the task. Smokers, but not former or non-smokers, maintained their gaze longer on e-cigarette than on neutral pictures ( p = 0.004). No difference in dwell time was found between device type. None of the smoking status groups showed faster initial fixations or faster reaction times to e-cigarette compared with neutral cues. Baseline craving was associated with dwell time on e-cigarette cues ( p = 0.004). Longer dwell time on e-cigarette cues was associated with more favorable attitudes towards e-cigarettes. These findings indicate that e-cigarette cues may contribute to craving for tobacco cigarettes and suggest the potential regulation of e-cigarette marketing.

Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior

Following a Pavlovian pairing procedure, alcohol-paired cues come to elicit behavioral responses that lead to alcohol consumption. Here we used an optogenetic approach to activate basolateral amygdala (BLA) axonal terminals targeting the shell of nucleus accumbens (AcbSh) and investigated a possible influence over cue-conditioned alcohol seeking and alcohol drinking, based on the demonstrated roles of these areas in behavioral responding to Pavlovian cues and in feeding behavior. Rats were trained to anticipate alcohol or sucrose following the onset of a discrete conditioned stimulus (CS). Channelrhodopsin-mediated activation of the BLA-to-AcbSh pathway concurrent with each CS disrupted cued alcohol seeking. Activation of the same pathway caused rapid cessation of alcohol drinking from a sipper tube. Neither effect was accompanied by an overall change in locomotion. Finally, the suppressive effect of photoactivation on cued-triggered seeking was also evidenced in animals trained with sucrose. Together these findings suggest that photoactivation of BLA terminals in the AcbSh can override the conditioned motivational properties of reward-predictive cues as well as unconditioned consummatory responses necessary for alcohol drinking. The findings provide evidence for a limbic-striatal influence over motivated behavior for orally consumed rewards, including alcohol.

Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels.

We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde) or there might be additional effects at central level. High drinker rats (UChB) were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day) or vehicle (as control) was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg) for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day) did not develop ethanol-conditioned place preference (CPP).In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol deprivation/re-access, and fenofibrate (50 mg/kg/day) was given only in deprivation periods; under this paradigm, fenofibrate was also able to generate a prolonged (30 days) decreasing of ethanol consumption, suggesting some effect beyond the acetaldehyde-generated aversion. In summary, reduction of ethanol intake by fenofibrate appears to be a consequence of a combination of catalase induction in the liver and central pharmacological effects.

Diverse Roads to Relapse: A Discriminative Cue Signaling Cocaine Availability Is More Effective in Renewing Cocaine Seeking in Goal Trackers Than Sign Trackers and Depends on Basal Forebrain Cholinergic Activity.

Stimuli associated with taking drugs are notorious instigators of relapse. There is, however, considerable variation in the motivational properties of such stimuli, both as a function of the individual and the nature of the stimulus. The behavior of some individuals (sign trackers, STs) is especially influenced by cues paired with reward delivery, perhaps because they are prone to process information via dopamine-dependent, cue-driven, incentive salience systems. Other individuals (goal trackers, GTs) are better able to incorporate higher-order contextual information, perhaps because of better executive/attentional control over behavior, which requires frontal cortical cholinergic activity. We hypothesized, therefore, that a cue that "sets the occasion" for drug taking (a discriminative stimulus, DS) would reinstate cocaine seeking more readily in GTs than STs and that this would require intact cholinergic neurotransmission. To test this, male STs and GTs were trained to self-administer cocaine using an intermittent access schedule with periods of cocaine availability and unavailability signaled by a DS+ and a DS-, respectively. Thereafter, half of the rats received an immunotoxic lesion that destroyed 40-50% of basal forebrain cholinergic neurons and later, after extinction training, were tested for the ability of noncontingent presentations of the DS+ to reinstate cocaine seeking behavior. The DS+ was much more effective in reinstating cocaine seeking in GTs than STs and this effect was abolished by cholinergic losses despite the fact that all rats continued to orient to the DS+ We conclude that vulnerability to relapse involves interactions between individual cognitive-motivational biases and the form of the drug cue encountered.SIGNIFICANCE STATEMENT The most predictable outcome of a diagnosis of addiction is a high chance for relapse. When addicts encounter cues previously associated with drug, their attention may be unduly attracted to such cues and these cues can evoke motivational states that instigate and maintain drug-seeking behavior. Although sign-tracking rats were previously demonstrated to exhibit greater relapse vulnerability to Pavlovian drug cues paired with drug delivery, here, we demonstrate that their counterparts, the goal trackers, are more vulnerable if the drug cue acts to signal drug availability and that the forebrain cholinergic system mediates such vulnerability. Given the importance of contextual cues for triggering relapse and the human cognitive-cholinergic capacity for the processing of such cues, goal trackers model essential aspects of relapse vulnerability.

The salience of a reward cue can outlast reward devaluation.

Reward cues can be perceived as highly attractive stimuli because of their acquired motivational properties. However, because the motivational value of reward changes after reward receipt, a debated question is whether the attentional salience of reward cues changes accordingly. In Experiment 1, thirsty participants learned 3 cue-reward associations involving different contingencies. Then, while thirsty, participants performed a visual-search task under extinction, during which the previous reward cues appeared as irrelevant stimuli containing target and distractor items. Experiment 2 was identical to Experiment 1, except that participants drank ad libitum before the visual-search task. In Experiment 3, instead, participants quenched their thirst at the beginning of the learning session. The results of Experiment 1 showed that attention was preferentially deployed toward the cue that best predicted the reward in the previous conditioning phase. Crucially, Experiment 2 revealed that the attentional bias persisted despite reward devaluation. By contrast, no attentional bias was found in Experiment 3. The novelty of our study is that the attentional salience of a reward cue can outlast reward devaluation, suggesting that some incentive properties of the cue can become independent from those of the reward. (PsycINFO Database Record

Pavlovian-to-Instrumental Transfer of Nicotine and Food Cues in Deprived Cigarette Smokers.

Smoking-related cues can promote drug-seeking behavior and curtail attempts to quit. One way to understand the potential impact of such cues is to compare cue-elicited behaviors for smoking and other reinforcers (eg, food) using the Pavlovian-to-instrumental transfer paradigm, which measures how much control cues can exert over reward-seeking responses. We tested the influence of appetitive cues on smokers' behavior following 12 hours of abstinence from smoking and eating. First, we equated the value of cigarette and food by assessing a Willingness-to-Pay measure for each reinforcer. Second, we evaluated behavioral differences between cues with Pavlovian-to-instrumental transfer. In two phases, participants learned (1) the association between distinct stimuli and cigarette or food outcomes and, (2) specific instrumental responses that yielded such outcomes. Motivated behavior was probed under extinction in a subsequent transfer test assessing instrumental responding in the presence of the cues. Participants showed an increase in specific responding (eg, instrumental response associated with cigarette) when faced with the corresponding appetitive cue (eg, stimulus associated with cigarette) despite absence of outcome. Notably, they made more cigarette-seeking than food-seeking instrumental responses, suggesting that cues representative of cigarette outcomes exert stronger influences on behavior than non-drug (food) cues. Using a measure of subjective preference, we also observed that greater preference for cigarette-compared to food-cues correlated with increased cigarette-seeking behavior in the test phase. Taken together, these results highlight how drug and non-drug cues differentially influence reward-seeking behaviors during deprivation, which has implications for smoking cessation treatment and relapse. This study examines the motivational influence of both drug and non-drug cues within a single sample of cigarette smokers. Our results demonstrate that the motivational properties of smoking cues differ from cues relating to other types of reward, such as food. This research informs smoking cessation programs to target the salience of nicotine cues and the maladaptive drug-seeking behaviors prompted by them.

Acetaldehyde, Motivation and Stress: Behavioral Evidence of an Addictive ménage à trois.

Acetaldehyde (ACD) contributes to alcohol’s psychoactive effects through its own rewarding properties. Recent studies shed light on the behavioral correlates of ACD administration and the possible interactions with key neurotransmitters for motivation, reward and stress-related response, such as dopamine and endocannabinoids. This mini review article critically examines ACD psychoactive properties, focusing on behavioral investigations able to unveil ACD motivational effects and their pharmacological modulation in vivo. Similarly to alcohol, rats spontaneously drink ACD, whose presence is detected in the brain following chronic self-administration paradigm. ACD motivational properties are demonstrated by operant paradigms tailored to model several drug-related behaviors, such as induction and maintenance of operant self-administration, extinction, relapse and punishment resistance. ACD-related addictive-like behaviors are sensitive to pharmacological manipulations of dopamine and endocannabinoid signaling. Interestingly, the ACD-dopamine-endocannabinoids relationship also contributes to neuroplastic alterations of the NPYergic system, a stress-related peptide critically involved in alcohol abuse. The understanding of the ménage-a-trois among ACD, reward- and stress-related circuits holds promising potential for the development of novel pharmacological approaches aimed at reducing alcohol abuse.

Estradiol is a critical regulator of food-reward behavior

Food intake is reduced by estrogenic hormones, levels of which vary throughout life and fluctuate throughout the ovarian cycle in females. However, estrogens have also been shown to increase reward derived from drugs of abuse, where motivational properties of drugs and progression to addiction are potentiated by estrogens. Whether reward derived from food, and specifically motivational properties of food, are altered by estrogens remains unknown. Here we investigated the effect of the estrous cycle on food reward behavior and show estrous cycle dictated variability in food motivation, measured by progressive ratio operant conditioning, in female rats. Reward behavior was lowest on days associated with high estrogen signaling. We therefore also examined the actions of subcutaneously administered β-estradiol on food reward and found that β-estradiol reduced food reward behavior. The ventral tegmental area (VTA) is a crucial node of the neurocircuitry underlying motivated behavior and estrogen receptors are expressed in this nucleus. Thus, we examined whether the effects of estrogens on reward were exerted directly at the level of the VTA. Intra-VTA microinjection of β-estradiol led to a significant reduction in food-motivated behavior. Interestingly, this effect was not accompanied by a reduction in chow intake or body weight, nor did it alter locomotor activity. Importantly, removal of the ovaries produced a potent and lasting elevation in food reward and food-seeking behavior, suggesting that ovarian sex steroids are critical for maintenance of normal food reward behavior. These data reveal a novel role for estrogens in the control of food reward behavior.​

Properties of the marijuana motives questionnaire among medical cannabis patients

Properties of the marijuana motives questionnaire among medical cannabis patients