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Rational: Stress is a major trigger for drug relapse in humans and animal models, even after prolonged abstinence. However, animal models for stress-induced relapse were criticized for the lack of predictive and face validity. Objectives: Here we investigated the effect of acute food deprivation stress in a novel stress-induced relapse model using voluntary, punishment-imposed abstinence from heroin. We also performed a detailed characterization of the development of punishment-imposed abstinence. Methods: Male rats were trained to self-administered heroin (0.1 mg/kg/infusion) for 2 weeks, using the seeking-taking chained schedule. Pressing the 'seeking' lever led to the insertion of the 'taking' lever and pressing the take lever resulted in heroin infusion. Following self-administration training, rats were exposed to 8 or 21 days of heroin-seeking punishment. During punishment, 30% of the completed seek links resulted in a mild escalating footshock instead of take lever presentation. Next, rats were tested for heroin seeking under extinction conditions after 24 h of food deprivation and sated conditions. Results: Probabilistic punishment of seeking lever responses resulted in gradual suppression of heroin seeking and taking. Exposure to food-deprivation stress induced a robust relapse to heroin seeking after short and long punishment-imposed abstinence periods, without significant effects of time, i.e., no incubation of heroin seeking. Individual differences were observed in the development of punishment-induced abstinence and stress-induced relapse. Conclusions: These results suggest that stress is a reliable trigger to relapse even after a prolonged period of punishment-induced, voluntary abstinence. [ABSTRACT FROM AUTHOR]

Objective: In the current study, we use functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA) to investigate whether tobacco addiction biases basic visual processing in favour of smoking-related images. We hypothesize that the neural representation of smoking-related stimuli in the lateral occipital complex (LOC) is elevated after a period of nicotine deprivation compared to a satiated state, but that this is not the case for object categories unrelated to smoking. Methods: Current smokers (≥10 cigarettes a day) underwent two fMRI scanning sessions: one after 10 h of nicotine abstinence and the other one after smoking ad libitum. Regional blood oxygenated level-dependent (BOLD) response was measured while participants were presented with 24 blocks of 8 colour-matched pictures of cigarettes, pencils or chairs. The functional data of 10 participants were analysed through a pattern classification approach. Results: In bilateral LOC clusters, the classifier was able to discriminate between patterns of activity elicited by visually similar smoking-related (cigarettes) and neutral objects (pencils) above empirically estimated chance levels only during deprivation (mean = 61.0%, chance (permutations) = 50.0%, p = .01) but not during satiation (mean = 53.5%, chance (permutations) = 49.9%, ns.). For all other stimulus contrasts, there was no difference in discriminability between the deprived and satiated conditions. Conclusion: The discriminability between smoking and non-smoking visual objects was elevated in object-selective brain region LOC after a period of nicotine abstinence. This indicates that attention bias likely affects basic visual object processing. [ABSTRACT FROM AUTHOR]

Background: Rats reared in social isolation exhibit various cognitive and behavioural abnormalities in adulthood. However, impulsivity following this treatment still remains unclear, especially in response to medications used in attention deficit hyperactivity disorder, such as amphetamine. Methods: Using an isolation-rearing (IR) manipulation, the present study examined the effects of IR on impulsive action and impulsive choice when also treated with doses of d-amphetamine, by employing the five-choice serial reaction time task (5-CSRTT) and a temporal discounting of reward task (TDRT), respectively. Results: IR rats showed similar acquisition of the 5-CSRTT. Amphetamine increased premature responding in both groups; however, IR rats showed less responding overall. For the TDRT, IR rats revealed a greater preference for the large but delayed reward during task acquisition (i.e. were less impulsive) with a higher rate of nose poking during the delay, and exhibited a compressed dose-response function (i.e. reduced dose sensitivity) for amphetamine. Discussion: Impulsive action and impulsive choice were reduced in IR rats under certain conditions, and a blunted response to d-amphetamine was found on these measures. These reductions in impulsivity contrast with locomotor hyperactivity normally shown in IR rats and the findings have implications for the utility of IR as a model of psychopathology. [ABSTRACT FROM AUTHOR]

Rationale: Alcohol addiction causes severe problems, and its deprivation may potentiate symptoms such as anxiety. Furthermore, ethanol is a neurotoxic agent that induces degeneration and the consequences underlying alcohol-mediated brain damage remain unclear. Objectives: This study assessed the behavioral changes during acute ethanol withdrawal periods and determined the levels of DNA damage and reactive oxygen species (ROS) in multiple brain areas. Methods: Male Wistar rats were subjected to an oral ethanol self-administration procedure with a forced diet where they were offered 8 % ( v/v) ethanol solution for 21 days followed by five repeated 24-h cycles alternating between ethanol withdrawal and re-exposure. Control animals received an isocaloric control diet without ethanol. Behavioral changes were analyzed on ethanol withdrawal days in the open-field (OF) and elevated plus-maze (EPM) tests within the first 6 h of ethanol deprivation. The pre-frontal cortex, hypothalamus, striatum, hippocampus, and cerebellum were dissected for alkaline and neutral comet assays and for dichlorofluorescein ROS testing. Results: The repeated intermittent ethanol access enhanced solution intake and alcohol-seeking behavior. Decreased exploratory activity was observed in the OF test, and the animals stretched less in the EPM test. DNA single-strand breaks and ROS production were significantly higher in all structures evaluated in the ethanol-treated rats compared with controls. Conclusions: The animal model of repeated intermittent ethanol access induced behavioral changes in rats, and this ethanol exposure model induced an increase in DNA single-strand breaks and ROS production in all brain areas. Our results suggest that these brain damages may influence future behaviors. [ABSTRACT FROM AUTHOR]

Rationale: Evidence based on clinical and experimental animal studies indicates that adolescent social deprivation influences alcohol consumption in a sex-dependent manner, perhaps by influencing stress responses. However, the mechanisms underlying the interaction between these phenomena remain to be elucidated. Since the μ-opioid receptor (MOP) has been reported to have key roles in social stress responses as well as the reinforcing/addictive effects of ethanol, MOP is a candidate molecule that may link adolescent social deprivation and subsequent alterations in alcohol consumption. Objectives: To evaluate the involvement of MOP and social isolation-induced changes in alcohol consumption, as well as the effect of sex differences on responses to social isolation, alcohol consumption was assessed using a two-bottle home-cage consumption procedure (8 % ethanol vs. water) in MOP knockout (MOP-KO) and wild type (WT) mice of both sexes exposed to adolescent social deprivation or reared socially. Results: Isolation rearing had no effects upon alcohol consumption of WT mice, whereas it significantly altered alcohol consumption in both male and female MOP-KO mice. Interestingly, social isolation affected ethanol consumption differently in male and female mice. Ethanol consumption was increased in male MOP-KO mice, but decreased in female MOP-KO mice, by isolation rearing. Conclusion: These results indicate that disturbances of MOP function influence the effects of isolation rearing on ethanol consumption in a sex-dependent manner. Consequently, this suggests the possibility that genetic variation that influences MOP function may have differential roles in alcoholism in men and women, and alcoholism treatments that target MOP function may be differentially effective in males and females. [ABSTRACT FROM AUTHOR]

Rationale: Limited access nicotine self-administration decreases hippocampal neurogenesis, providing a mechanism for the deleterious effects of nicotine on hippocampal neuronal plasticity. However, recent studies have shown that limited access nicotine self-administration does not exhibit key features of nicotine dependence such as motivational withdrawal and increased motivation for nicotine after deprivation. Objectives: The present study used extended access nicotine self-administration (0.03 mg/kg/infusion, 21 h/day, 4 days) with intermittent periods of deprivation (3 days) for 14 weeks, to test the hypothesis that this model enhances nicotine seeking and produces distinct responses in hippocampal neurogenesis when compared with limited access (1 h/day, 4 days) intake. Animals in the extended access group were either perfused prior to or following their final deprivation period, whereas animals in the limited access group were perfused after their last session. Results: Limited- and extended access nicotine self-administration with periodic deprivation did not affect proliferation and differentiation of oligodendrocyte progenitors in the medial prefrontal cortex (mPFC). Conversely, extended access nicotine self-administration with periodic deprivation enhanced proliferation and differentiation of hippocampal neural progenitors. Furthermore, in the hippocampus, the number of differentiating NeuroD-labeled cells strongly and positively correlated with enhanced nicotine seeking in rats that experienced extended access nicotine self-administration. Conclusions: These findings demonstrate that extended versus limited access to nicotine self-administration differentially affects the generation of new oligodendroglia and new neurons during adulthood. The increases in the number of differentiating cells in extended access nicotine self-administering rats may consequently contribute to aberrant hippocampal neurogenesis and may contribute to maladaptive addiction-like behaviors dependent on the hippocampus. [ABSTRACT FROM AUTHOR]

Rationale: It is well established that nicotine improves, and deprivation impairs, cognitive performance and mood in smokers. Prospective memory (PM), remembering to execute a delayed intention at a given time point, is under-explored in smokers. Whilst a handful of studies have shown improved PM with nicotine, the effects of nicotine delivered via the electronic cigarette (e-cigarette) have not been investigated. Objective: This study explores whether, by comparison with placebo, nicotine delivered via the e-cigarette can improve PM, tobacco withdrawal symptoms and desire to smoke in abstinent smokers. Methods: Twenty smokers, abstinent for 8-10 h, each completed two experimental sessions under nicotine (18 mg) and placebo (0 mg) e-cigarette conditions. Participants completed a single-item desire-to-smoke scale and the Mood and Physical Symptoms Scale. PM was measured using the Cambridge Prospective Memory Test. Results: Compared with placebo, the nicotine e-cigarette reduced the desire to smoke and tobacco withdrawal symptoms, and improved time-based but not event-based PM. There was a moderate, marginally significant negative correlation between PM performance during abstinence and nicotine dependence. Conclusions: This is the first study to show that nicotine derived via e-cigarette can improve PM in abstinent smokers, suggesting efficient nicotine delivery. The finding that the effect of nicotine was restricted to time-based rather than event-based PM is consistent with the view that nicotine acts to improve performance on strategic (effortful) rather than automatic processing. These findings add to the growing body of evidence that the e-cigarette can replace some of the effects of nicotine derived from tobacco smoking, thus highlighting its potential for smoking cessation. [ABSTRACT FROM AUTHOR]

Rationale and objectives: Previous research with an animal model of relapse has shown that acute food deprivation will reinstate extinguished drug seeking. Recent evidence with humans, however, suggests that chronic food restriction rather than acute food deprivation is related to increases in drug taking and relapse, emphasizing a need for an animal model to elucidate the neural mechanisms mediating the effects of chronic food restriction on drug seeking. Here we studied the effects of chronic food restriction during a period of abstinence on heroin seeking in rats. Methods: Rats were trained to self-administer heroin over 10 days (0.1 mg/kg/infusion; i.v.). Rats were then removed from the operant conditioning chambers and exposed to a mild food restriction (resulting in 10-15 % decrease in body weight) or given unrestricted access to food for 14 days while abstinent. The abstinence period was followed by a drug-seeking test under extinction conditions. Subsequent experiments manipulated the length of restriction and test conditions. Results: Rats that were food restricted throughout the abstinence period demonstrated a robust increase in cue-induced heroin seeking compared to sated rats. Re-feeding prior to testing or decreasing the length of the food restriction period prevented the augmentation of drug seeking. Conclusions: A combination of chronic food restriction and a concurrent state of hunger appears to be necessary for an increase in cue-induced heroin seeking following abstinence. The procedure presented here may serve as a useful model to study the increased risk for relapse following dietary manipulations in abstinent subjects. [ABSTRACT FROM AUTHOR]

Higher rates of delay discounting, or impulsive choice, may be related to relapse during abstinence reinforcement interventions for cigarette smoking, and a transdermal nicotine patch may attenuate delay discounting. The objectives of this study are to assess the relation between delay discounting and smoking after nicotine deprivation in a laboratory model of abstinence reinforcement and the effects of a transdermal nicotine patch on discounting and smoking. Smokers with no self-reported intention to quit were randomly assigned to an active (14 mg) or placebo patch group ( n = 15 per group). In each of three sessions, after a 3-h deprivation period, participants completed a delay discounting task, mood, and craving measures and finally engaged in a laboratory model of abstinence reinforcement. Three abstinence reinforcement conditions were presented in counterbalanced order across the three sessions. During the control session, monetary consequences were delivered every 30 s regardless of smoking. During the low ($5.00 available) and high ($20.00 available) sessions, participants could earn a progressively increasing amount of money for each 30 s period of abstinence. The low and high conditions significantly increased the latency to smoke relative to control and significantly decreased the amount of smoking. The nicotine patch decreased negative affect, but it did not significantly affect delay discounting or smoking. Individuals who smoked during the low and high conditions showed higher rates of discounting. The patch did not attenuate delay discounting or smoking after a period of deprivation, but contingencies for abstinence significantly decreased smoking. Higher rates of delay discounting were related to smoking in a model of abstinence reinforcement treatment. [ABSTRACT FROM AUTHOR]

In smokers, nicotine deprivation may increase impulsive decision-making and the demand for cigarettes. Objectives: To investigate the effects of acute nicotine deprivation on (a) the delay discounting of monetary and cigarette rewards, and (b) the behavioural economics of hypothetical cigarette purchases. Materials and methods: A repeated measures design was employed, with participants (daily cigarette smokers, N=30) repeating experimental tasks in two different sessions, once after at least 13 h of abstinence from smoking and once after ad lib smoking. Participants completed measures of cigarette craving, impulsivity, delay discounting and a behavioural economic simulation in which participants made hypothetical purchases of cigarettes and other commodities as the price of cigarettes was systematically varied. Results: Participants showed more pronounced delay discounting of both cigarette and monetary rewards after abstinence compared to after ad lib smoking. In the behavioural economic simulation, nicotine deprivation had no influence on hypothetical cigarette purchases. However, spending on some commodities (alcohol, clothing, household goods, leisure activities and long-distance travel) was reduced as the price of cigarettes increased in order to fund increased spending on cigarettes, although the number of packs of cigarettes purchased actually decreased. Conclusions: Nicotine deprivation increases impulsive choices for both cigarette and monetary rewards in a delay-discounting task. Results from a behavioural economic simulation suggest that increases in the price of cigarettes may increase smokers' spending on cigarettes, while also reducing the number of cigarettes purchased. [ABSTRACT FROM AUTHOR]

Rationale: Animal models that identify the effects of self-administration histories on subsequent patterns, levels of intake, and other aspects of reinforcement will help clarify the controlling variables of human drug use. Objective: Identify the effects of extended-access to cocaine and 1 or 7 days of deprivation on cocaine-maintained breakpoints on a progressive ratio (PR) schedule of reinforcement. Methods: Male, Sprague--Dawley rats were trained to self-administer intravenous cocaine (expt 1: 1.5 mg/kg per infusion; expt 2: 0.75 mg/kg per infusion), and then given various histories of self-administration and deprivation. Breakpoints, the number of infusions self-administered on a PR schedule, were assessed following the deprivation period. Results: Rates of cocaine intake increased when access to cocaine was extended to 6 h/day. From day 1 to day 14, daily intake increased from 92 (±2.5) to 101 (±2.8) mg/kg in expt 1, and from 55 (±4) to 78 (±2.2) mg/kg in expt 2. Total intake across this 2-week period was approximately 1260 and 970 mg/kg in expts 1 and 2. Breakpoints were not different following this escalation period. The introduction of a 7-day deprivation period failed to alter breakpoints. Conclusions: There is dissociation between changes in rate of cocaine intake (or consumption) and breakpoints maintained on a PR schedule. Extended-access to cocaine produced increases in rate of intake without altering breakpoints. Depending on the experimental question, extended-access conditions may prove useful for studying changes in certain aspects of reinforcement, such as consumption, but not others, such as the strength of a drug as a reinforcer. [ABSTRACT FROM AUTHOR]

Presents a study on the effects of cocaine self-administration and deprivation on rats. Objectives of the study; Study methods; Results.

Rationale: Most studies of the effects of caffeine on performance have used regular caffeine consumers who are deprived at test. Thus the reported effects of caffeine could be explained through reversal of caffeine withdrawal. Objectives: To test how preloading deprived caffeine consumers with 0, 1 or 2 mg/kg caffeine altered the subsequent ability of caffeine to modify mood and performance. Methods: Thirty moderate caffeine consumers were given a drink containing 0, 1 or 2 mg/kg caffeine at breakfast followed 60 min later by a second drink containing either 0 or 1 mg/kg caffeine. Performance on a measure of sustained attention and mood were measured before and after each drink. Results: Administration of both 1 and 2 mg/kg caffeine at breakfast decreased reaction time and 1 mg/kg caffeine also increased performance accuracy on the sustained attention (RVIP) task relative to placebo. Both breakfast doses of caffeine also improved rated mental alertness. Similarly, 1 mg/kg caffeine administered 60 min after breakfast decreased reaction time and increased rated mental alertness in the group who had not been given caffeine at breakfast. However, this second dose of caffeine had no effect on subsequent performance or mood in the two groups who had received caffeine at breakfast. Conclusions: Caffeine reliably improved performance on a sustained attention task, and increased rated mental alertness, in moderate caffeine consumers who were tested when caffeine-deprived. However, caffeine had no such effects when consumers were no longer caffeine deprived. These data are consistent with the view that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Intermittent footshock reinstates drug-taking behavior in rats, but not behaviors previously maintained by food reinforcers. Here we tested further the generality of this phenomenon by determining whether restraint and food deprivation stressors would reinstate heroin seeking, whether the environment in which footshock is given modulates footshock-induced reinstatement, and whether footshock would reinstate operant responding previously maintained by brain stimulation reward (BSR). Methods: Groups of rats were trained to self-administer for 10 days either heroin (0.05-0.1 mg/kg/infusion, IV, three 3-h sessions/day) or brain stimulation into the septal area (trains of monopolar cathodal pulses of 100 micro s for 500 ms, one 60-min session/day). After extinction of the heroin-reinforced behavior (10-13 days), the rats were tested for reinstatement after exposure to food deprivation (1 and 21 h), restraint given outside the self-administration environment (5, 15 and 30 min), or intermittent footshock (0.8 mA, 15 min) given in the self-administration environment or in a novel (non-drug) environment. For BSR-trained rats, the effect of footshock on reinstatement alter extinction (6-10 days) was compared with that induced by noncontingent brain stimulation (three or six discrete stimulations at the start of the test sessions). Results: Food deprivation reinstated heroin seeking. Footshock reliably reinstated heroin seeking when given in the drug environment, but not when given in a non-drug environment. Similarly, restraint given outside the sell-administration environment failed to reinstate heroin seeking. In addition, footshock was as effective as priming brain stimulation in reinstating operant responding previously maintained by BSR. Conclusions: The effect of footshock on reinstatement of heroin seeking generalizes to food deprivation, and appears to be dependent on the environment in which the stressor is given. The data with BSR indicate that [ABSTRACT FROM AUTHOR]

Presents information on a study that adopted a chronic mild stress (CMS) schedule. Discussion on related studies; Observation on the omission of the food deprivation component of the CMS procedure; Effect of chronic mild stress on saccharin intake in food-deprived and non food-deprived rats.