Attenuation of response to drug-related cues in male heroin abstainers is modulated by cognitive control mechanisms

Background: Many research studies reveal that both attentional bias and impaired cognitive control significantly influence heroin addiction. However, limited research has been conducted into how the interplay between attentional bias and cognitive control modulates heroin-seeking behavior. Objectives: A modified version of the flanker task was used to investigate whether attentional bias to drug-related stimuli is modulated by cognitive control mechanisms among heroin users. Methods: Sixty participants (30 male heroin users during their abstinence period and 30 normal controls) responded to the direction of the middle arrow, while ignoring the adjacent arrow and the pictures (drug-related cues and neutral cues) presented as part of the task. Results: The abstinent heroin users had a significantly larger flanker effect under drug-related cues compared to neutral cues, whereas the control group showed no such trend. This effect was primarily influenced by increased reaction times in the presence of drug-related cues relative to neutral cues in the incongruent condition among abstinent heroin users, but not in the control group. Conclusions/Importance: Among abstinent heroin users, attentional bias to drug-related cues was moderated by attentional control. Further, high cognitive control demand was found to reduce heroin users’ ability to resist attentional capture from salient, but irrelevant, drug-related information, which may contribute to compulsive drug-seeking behavior and relapse in heroin users.     

Stress Enhances Retrieval of Drug-Related Memories in Abstinent Heroin Addicts

Stress is associated with relapse to drugs after abstinence, but the mechanisms for this association are unclear. One mechanism may be that stress enhances abstinent addicts'' recall of memories of drugs as stress relievers. This study assessed the effects of stress on free recall and cued recall of 10 heroin-related and 10 neutral words learned 24 h earlier by 102 abstinent heroin addicts. These participants were randomly assigned to three experiments that also assessed attention and working memory. Experiment 1 used a psychosocial stressor (Trier social stress test (TSST)) before testing for recall of heroin-related words. Experiment 2 added administration of the β-adrenoceptor antagonist propranolol 1 h before the psychosocial stressor. Experiment 3 added administration of either cortisol with propranolol, cortisol alone, or propranolol alone 1 h before word recall to determine whether stress enhancement of heroin-related word recall required noradrenergic-glucocorticoid interactions. We found that free recall of heroin-related words in abstinent addicts was enhanced after stress or cortisol administration when compared with a non-stress condition or placebo, respectively, whereas these interventions had no effect on neutral word recall. β-adrenergic blockade blocked the enhancing effect of stress or cortisol on free recall of heroin-related words. Neither stress nor cortisol affected cued recall, attention, or working memory. The potential of β-adrenergic blockade to reduce or block stress-induced enhancement of drug-related memory retrieval may be relevant to preventing stress-induced relapse in abstinent heroin addicts.     

Behavioural approach tendencies to heroin-related stimuli in abstinent heroin abusers

Rationale

Drug-related cues can elicit approach responses in drug users. However, no relevant research has ever concerned heroin abusers. In the present study, we investigated whether the abstinent heroin abusers demonstrated special behavioural tendencies to approach or avoid the drug-related stimuli compared with neutral stimuli.

Method

Twenty-two male abstinent heroin abusers (AH) and 20 healthy males (NC) were tested by a Pull/Push Task. Participants pulled (approach response) or pushed (avoidance response) a lever in response to the content of stimulus pictures (i.e. heroin-related versus neutral). The approach and avoidance scores were therefore calculated based on response times and directions to reflect their behavioural tendencies.

Results and conclusion

Relative to the NC individuals, the AH individuals demonstrated significantly heightened tendencies to approach (“pull”) the heroin-related stimuli in comparison with the neutral stimuli, while their tendencies to avoid (“push”) the heroin-related stimuli were marginally blunted, reflecting a special bias for AH individuals to behaviourally approach, and simultaneously resist to avoid, heroin-related cues.     

Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking

RATIONALE: In smokers, pictures of smoking that increase desire for a cigarette are described as pleasant rather than unpleasant. This suggests that these smoking cues may be appetitive and not withdrawal-like or aversive as held by traditional theories of drug cue formation. OBJECTIVE: Cues for smoking were examined using physiological measures of motivational valence. METHODS: Non-deprived smokers, deprived smokers and deprived smokers who expected to smoke (n=54) viewed a computer screen presenting experimental and control scenes (experiment 1). The acoustic startle reaction and activity of the corrugator and the zygomatic facial muscles were then measured after onset of smoking cues and standardized pleasant, neutral or unpleasant control scenes. Individuals who never smoked (n=18) were also used to test for cue effects on startle (experiment 2). RESULTS: No evidence was found that smoking cues were aversive in smokers. The smoking cues affected the startle responses and corrugator activity in a way similar to that of pleasant control material but significantly different from that of unpleasant material; the cue effects on zygomatic activity was most similar to that of neutral material. The general pattern of effects was not influenced by overnight smoke deprivation, expectancy to smoke or smoke repletion, but it was different in never smokers where the smoking scenes were found to be similar to unpleasant control scenes. CONCLUSIONS: Nonsubjective measures of motivational valence further suggest that drug cues are conditioned stimuli having appetitive effects. Startle response modulated by drug cues may be useful for probing motivational processes underlying dependence in the human.     

海洛因依赖者操守成败相关因素的调查分析

目的:探讨海洛因依赖者操守成败的相关因素及预防复吸的对策。方法:问卷调查35名戒毒后操守12个月以上及36名屡戒不成的海洛因依赖者,比较两组的人口学资料,操守成败相关因素。结果:成功操守者吸毒时间相对较短(P<0.01);戒毒次数和接受替代治疗相对较少(P<0.01);吸毒前对毒品认识不足(P<0.05)及因吸毒而受到的法律制裁较多(P<0.05)。维持操守的主要因素是正确的认知;而失败的因素是未脱离吸毒环境。结论:维持操守主要与正确的认知有关,据此制定综合性的预防复吸措施。     

Cue-Elicited Craving in Heroin Addicts at Different Abstinent Time: An fMRI Pilot Study

Objective: We evaluated the effect of short-term and long-term heroin abstinence on brain responses to heroin-related cues using functional magnetic resonance imaging (fMRI). Methods: Eighteen male heroin addicts following short-term abstinence and 19 male heroin addicts following long-term abstinence underwent fMRI scanning while viewing heroin-related and neutral images. Cue-elicited craving and withdrawal symptoms in the subjects were measured. Results: Following short-term abstinence, greater activation was found in response to heroin cues compared to neutral cues in bilateral temporal, occipital, posterior cingulate, anterior cingulate, thalamus, cerebellum, and left hippocampus. In contrast, activations in bilateral temporal and occipital and deactivations in bilateral frontal, bilateral parietal, left posterior cingulate, insula, thalamus, dorsal striatum, and bilateral cerebellum were observed following long-term abstinence. Direct comparisons between conditions showed greater brain reactivity in response to smoking cues following short-term abstinence. In addition, short-term abstinence had more serious withdrawal symptoms than the long-term. Conclusion: The present findings indicate that compared to short-term, long-term abstinence manifests less serious withdrawal symptoms and significantly decreases neural responses to heroin-related cues in brain regions subserving visual sensory processing, attention, memory, and action planning. These findings suggest that long-term abstinence can decrease the salience of conditioned cues, thereby reducing the risk of relapses. The study's limitations are noted.     

Does recovery-oriented treatment prompt heroin users prematurely into detoxification and abstinence programmes? Qualitative study

Aims(i) To consider whether or not recovery-oriented treatment might be prompting heroin users prematurely into detoxification and abstinence programmes; (ii) to explore the findings with reference to Foucauldian theory.MethodsLongitudinal qualitative data comprising 57 audio-recorded interviews, which captured heroin users’ views and experiences of treatment duration. Participants included 30 heroin users (15 men; 15 women) starting a new episode of treatment, of whom 27 (14 men; 13 women) were re-interviewed after 3 months. Recruitment occurred in community drug services, pharmacies and residential treatment settings in Southern England, UK. Transcribed data were systematically coded and analysed inductively.FindingsAll participants wanted to be free from heroin and prescribed substitute drugs. Individuals were often impatient with the detoxing process and some reduced dosages of substitute medication faster than prescribers recommended, occasioning cross addiction and relapse. Previously unsuccessful rapid detoxifications induced slower recovery attempts. Participation in residential rehabilitation facilitated client realisation that recovery required time and effort.ConclusionsRecovery-oriented treatment can prompt heroin users prematurely into detoxification and abstinence programmes with negative consequences. The desire to detoxify quickly can be interpreted through Foucault's concepts of ‘self-governance’ and ‘resistance;’ heroin users’ participation in decision-making processes reflects notions of ‘agency;’ and clients’ willingness to adopt longer approaches to recovery following past negative detoxification experiences and exposure to residential rehabilitation confirms their commitment to be ‘well.’ The experiential knowledge of heroin users who have personally attempted recovery is a crucial resource for both those contemplating their own recovery and those advocating recovery-oriented services.     

Attentional and evaluative biases for smoking cues in nicotine dependence: component processes of biases in visual orienting

The present study investigated attentional and evaluative biases for smoking-related cues in cigarette smokers and non-smokers. Using a visual probe task, we manipulated the presentation conditions of the stimuli to examine: (1). whether smokers have a bias to allocate attention towards smoking-related pictures that appear below the threshold of conscious awareness; and (2). whether attentional biases for smoking-related pictures that appear above the threshold of awareness operate both in initial orienting and in the maintenance of attention. We also obtained explicit and implicit measures of the valence of the smoking-related pictures from pleasantness ratings and from behavioural responses on a stimulus-response compatibility (SRC) task. Results showed that smokers, but not non-smokers, had an attentional bias for smoking-related pictures which had been presented at two exposure durations (200 and 2000 ms). The bias was not found in a brief (17 ms) masked exposure condition, so there was no evidence that it operated preconsciously. Smokers also showed greater preferences for smoking-related than control cues, compared with non-smokers, on both the explicit and implicit indices of stimulus valence. Results are discussed with reference to incentive and cognitive models of addiction.     

μ-Opioid receptor availability in the amygdala is associated with smoking for negative affect relief

Rationale

Relapse is a persistent problem in the management of addiction. Drug-related cues are powerful instigators of relapse. Impulsive decision making may contribute to relapse through a poorly considered assessment of the consequences of drug use. Drug cues robustly increase subjective craving, which is frequently associated with relapse.

Objective

The present study explored the effects of drug-related cues on decision making and craving in heroin addicts at different abstinence times: 1, 3, 12, and 24?months.

Methods

The 75 male participants were given 5?min exposure to neutral and drug-associated cues while decision making performance, craving, blood pressure, heart rate, and emotional state pre- and post-exposure were assessed. The Iowa Gambling Task was used to evaluate decision making ability in heroin addicts.

Results

Drug-related cues exacerbated impulsive decision making and increased craving, heart rate, and systolic pressure in heroin addicts at all abstinence times.

Conclusions

Drug-related cues aggravated decision making and increased craving in former heroin addicts who had been drug-free for 1–24?months, which might have significant clinical implications for the prevention of relapse.     

Lack of startle modulation by smoking cues in smokers

Rationale The startle reflex methodology has been used to study the effects of nicotine in humans and the motivational effects of smoking cues in smokers. However, no other studies investigate startle modulation by smoking cues in smokers compared to non-smokers. In the other studies, smoking deprivation was manipulated in smokers or smokers were not compared directly to non-smokers.Objective The goal of this study was to examine the temporal course of information processing following the presentation of a smoking-related cue using the startle probe methodology in smokers compared to non-smokers.Methods Thirty-four smokers were selected on the basis of nicotinic dependence according to the DSM-IV, and compared to 34 non-smokers. During testing, subjects viewed neutral pictures and smoking related pictures displayed on a computer screen. Acoustic startle stimuli were delivered at various times after picture onset (60, 120 or 5000 ms) to examine inhibition by lead stimulus and the affective modulation of startle.Results The magnitude of startle reflex inhibition increased in smokers compared to non-smokers, at 60 and 120 ms. In all, there was no Picture×Group interaction effect.Conclusion We showed that smoking cues have no impact on the startle reflex of either group, even if, in line with previous results, prepulse inhibition was higher in smokers than non-smokers. These results suggest that smoking cues have no effect on the positive reinforcement of nicotine consumption, and that cognitive factors play a primary role in the development and maintenance of tobacco dependence.     

24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum

Rationale  Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence. Objectives  In the present study, we evaluated the effect of 24-h smoking abstinence on brain responses to smoking-related cues using functional magnetic resonance imaging (fMRI). Materials and methods  Eighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-h abstinence (abstinent condition). During scanning, they viewed blocks of photographic smoking and control cues. Results  Following abstinence, greater activation was found in response to smoking cues compared to control cues in parietal (BA 7/31), frontal (BA 8/9), occipital (BA 19), and central (BA 4) cortical regions and in dorsal striatum (putamen) and thalamus. In contrast, no smoking cue greater than control cue activations were observed following smoking as usual. Direct comparisons between conditions (satiated vs. abstinent) showed greater brain reactivity in response to smoking cues following abstinence. In addition, positive correlations between pre-scan craving in the abstinent condition and smoking cue activation were observed in right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA 6/10), anterior cingulate gyrus (BA 32), and supplementary motor area (BA 6). Conclusions  The present findings indicate that smoking abstinence significantly potentiates neural responses to smoking-related cues in brain regions subserving visual sensory processing, attention, and action planning. Moreover, greater abstinence-induced craving was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision making. These findings suggest that drug abstinence can increase the salience of conditioned cues, which is consistent with incentive-motivation models of addiction. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Psychosocial stress after reactivation of drug-related memory impairs later recall in abstinent heroin addicts

Introduction  Stress and stress hormone are known to play important roles in modulating different stages of memory including reconsolidation. In a previous study, we found that treatment with stress or corticosterone after a single memory reactivation disrupted reconsolidation of a drug-related memory in rats. Here we presumed that stress after memory reactivation can effectively inhibit drug-related memory by disrupting its reconsolidation in abstinent heroin addicts. Materials and methods  In the present study, 21 abstinent heroin addicts learned a word list (containing ten neutral, ten heroin-related negative, and ten heroin-related positive words) on day 1; retrieval of a word list (learned 24 h earlier) was made on day 2; and immediately after retrieval, they were exposed to either a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control condition in a crossover manner. On day 3, free recall of the word list and other psychological and physical responses were assessed. Results  The stressor induced a significant increase in salivary free cortisol and a decrease in mood. Memory recall was significantly impaired after the stress condition. Follow-up analysis revealed that heroin-related negative and positive words (i.e., heroin-related words) were affected, whereas no effect was observed for neutral words. No changes were detected for cued recall, working memory, or attention. Stress after drug-related memory retrieval significantly decreased its subsequent recall, likely through impaired drug-related memory reconsolidation process. Conclusion  Reconsolidation blockade may thus provide a potential therapeutic strategy for the prevention of relapse in drug addiction.     

Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin Seeking

Successful treatment of drug addiction is hampered by high relapse rates during periods of abstinence. Neuroadaptation in the medial prefrontal cortex (mPFC) is thought to have a crucial role in vulnerability to relapse to drug seeking, but the molecular and cellular mechanisms remain largely unknown. To identify protein changes that contribute to relapse susceptibility, we investigated synaptic membrane fractions from the mPFC of rats that underwent 21 days of forced abstinence following heroin self-administration. Quantitative proteomics revealed that long-term abstinence from heroin self-administration was associated with reduced levels of extracellular matrix (ECM) proteins. After extinction of heroin self-administration, downregulation of ECM proteins was also present in the mPFC, as well as nucleus accumbens (NAc), and these adaptations were partially restored following cue-induced reinstatement of heroin seeking. In the mPFC, these ECM proteins are condensed in the perineuronal nets that exclusively surround GABAergic interneurons, indicating that ECM adaptation might alter the activity of GABAergic interneurons. In support of this, we observed an increase in the inhibitory GABAergic synaptic inputs received by the mPFC pyramidal cells after the re-exposure to heroin-conditioned cues. Recovering levels of ECM constituents by metalloproteinase inhibitor treatment (FN-439; i.c.v.) prior to a reinstatement test attenuated subsequent heroin seeking, suggesting that the reduced synaptic ECM levels during heroin abstinence enhanced sensitivity to respond to heroin-conditioned cues. We provide evidence for a novel neuroadaptive mechanism, in which heroin self-administration-induced adaptation of the ECM increased relapse vulnerability, potentially by augmenting the responsivity of mPFC GABAergic interneurons to heroin-associated stimuli.     

Cue-induced craving and physiological reactions in recently and long-abstinent heroin-dependent patients

Objective

To understand the different patterns of cue-induced craving and physiological reactions among recently abstinent and long-abstinent heroin-dependent patients.

Method

26 healthy adult controls (HC), 29 long-abstinent (more than 1 year, LA), and 26 recently abstinent (less than 1 month, RA) heroin-dependent individuals were exposed to heroin-related and neutral video cues, one video per session, on different days in random order. Self-reported heroin craving by a 10-point visual analog scale (VAS), physiological reactions [skin conductance (SC), muscle electromyography (MEG), skin temperature (TEMP)] and cardiovascular arousal [heart rates (HR), systolic blood pressure (HBP) and diastolic blood pressure (LBP)] were assessed at baseline and after exposure.

Results

Both heroin-abstinent groups showed increased heroin craving, SC, MEG, HR, SBP and LBP after exposure to heroin-related video, compared to the control group and compared to exposure to the neutral video. Except the RA group showed more HR changes, changes of heroin craving, SC, MEG, HR, SBP and LBP after exposure to the heroin cue video were not different between the LA and RA groups.

Conclusions

Abstinent heroin-dependent patients had elevated craving and physiological reactions after exposure to videos containing heroin-related cues and the cue induced responses still occurred in long-abstinent patients. This phenomenon should be addressed in treatment and recovery services for heroin dependence.     

Dysregulation of emotional response in current and abstinent heroin users: negative heightening and positive blunting

OBJECTIVE: Evidence suggests that abstinent opioid users have abnormal emotional response to natural reinforcing stimuli, but little is known about the emotional response of subjects currently using heroin. Abnormal emotional experience could underlie poor sensitivity to negative events related to heroin use and reduced ability to consider alternative reinforcers to help overcome addiction. In this paper, we will assess the subjective response of current and abstinent heroin users exposed to emotionally competent positive and negative stimuli. MATERIALS AND METHODS: We administered the "Clinical Instrument for Emotional Response Evaluation" (including neutral, pleasant, and unpleasant images from the International Affective Picture System) to 22 current opioid users enrolled in a clinical trial using controlled prescribed heroin and 41 abstinent opioid users enrolled in residential treatment. The dependent variable was their subjective response to the images measured with the Self-Assessment Manikin, a scale designed to rate the International Affective Picture System (IAPS) images in the three dimensions of emotion: valence, arousal, and dominance. We compared these ratings with IAPS normative values for healthy participants. RESULTS: Significant group x emotional condition interactions were found in the arousal dimension. Post-hoc tests showed that compared to healthy participants, both current and abstinent heroin users had greater emotional response to neutral images and lower response to pleasant images. Furthermore, current opioid users had higher emotional response to unpleasant images when compared to healthy participants and lower response to pleasant images when compared to abstinent users. CONCLUSIONS: Current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli.     

Automatic approach bias towards smoking cues is present in smokers but not in ex-smokers

Rationale

Drug-addicted individuals show automatic approach tendencies towards drug-related cues, i.e., an approach bias (ApB). Nevertheless, little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence.

Objectives

We investigated ApB to smoking cues in heavy tobacco smokers versus never-smokers and studied its relation to smoking characteristics and craving. Second, we compared ApBs of heavy smokers with biases of abstinent heavy smokers.

Method

A group of current heavy smokers (n?=?24), ex-smokers who were abstinent for at least 5 years (n?=?20), and never-smokers (n?=?20) took part in the experiment. An indirect smoking approach avoidance task was performed, in which participants were required to respond to pictures of smoking and neutral cues by pulling (approach) or pushing (avoid) on a joystick, according to the content-irrelevant format of the picture (landscape or portrait). Craving scores were examined using the Questionnaire of Smoking Urges.

Results

Heavy smokers showed an ApB for smoking cues compared to ex-smokers and never-smokers, which correlated positively to craving scores. There were no group differences in ApB scores for ex-smokers and never-smokers.

Conclusion

These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long-term successful smoking cessation.     

Affective reactivity during smoking cessation of never-quitters as compared with that of abstainers, relapsers, and continuing smokers

Much effort has been devoted to examining the differences in postcessation affective experience between smoking abstainers and relapsers. However, little attention has been given to the affective changes of smokers who, despite their motivation to quit, fail to achieve even a brief period of abstinence. Using affect-modulated startle response and self-report questionnaires, we measured the postcessation affective changes of 115 smokers (60 men, 55 women) who participated in a laboratory investigation of affective reactivity during smoking cessation. Among our participants, 34 were abstainers (16 men, 18 women), 16 were never-quitters (8 men, 8 women), 19 were relapsers (8 men, 11 women), and 46 were controls (28 men, 18 women). We found a significant Stimulus Valence × Session × Group interaction effect on startle responses, which suggested that while abstainers, relapsers, and control exhibited the prototypical affect-modulated startle response across postcessation sessions, never-quitters displayed an atypical response pattern in which emotional pictures no longer modulated the startle response. Never-quitters also reported increasingly higher negative and lower positive affect across postcessation sessions. Using affect-modulated startle response and self-report questionnaires, this study found a significant difference in the affective reactivity between smokers who could and smokers who could not establish an initial abstinence of 24 hours.     

Do the affective properties of smoking-related cues influence attentional and approach biases in cigarette smokers?

Research indicates that drug-related cues elicit attention and approach biases in drug users. However, attentional biases are not unique to addiction (e.g., they are also found for emotional information). This study examined whether attentional and approach biases in cigarette smokers are mediated by the motivational salience of cues (relevance to drug-taking), rather than by their affective properties (subjective liking of the cues). Cues included pleasant and unpleasant smoking-related pictures. Attentional biases, approach tendencies and subjective evaluation of the cues were assessed on visual probe, stimulus-response compatibility and rating tasks, respectively. Compared with non-smokers, smokers showed a greater attentional bias for both pleasant and unpleasant smoking-related cues presented for 2000 ms, but not for 200 ms. Smokers showed a greater approach bias for unpleasant cues, although the groups did not differ significantly in approach bias for pleasant smoking-related cues. Smokers rated both pleasant and unpleasant smoking pictures more positively than did non-smokers. Results suggest that a bias to maintain attention on smoking-related cues in young adult smokers is primarily a function of drug-relevance, rather than affective properties, of the cues. In contrast, approach tendencies and pleasantness judgements were influenced by drug use, drug-relevance and the affective properties of the cues.     

The effects of smoking and abstinence on experience of happiness and sadness in response to positively valenced, negatively valenced, and neutral film clips

Incentive motivation theories of addiction suggest that behavioural concomitants of compromised mesocorticolimbic reward activity during abstinence might include decreased affective reactions to natural reinforcers. This study tested implications for hedonic reactions in abstinent smokers. It was hypothesised that positively valenced (pleasurable) film clips would elicit lower ratings of happiness in abstinent than satiated smokers. Twenty-nine smokers, randomly assigned to either an 'abstinent' or a 'satiated' condition, and 15 non-smokers took part in a single session in which they rated (i) signs and symptoms of nicotine withdrawal and (ii) affective responses to positively valenced, negatively valenced, and neutral film clips. Compared with satiated smokers, abstinent smokers rated positive clips as eliciting significantly lower levels of happiness, and this was independent of self-reported nicotine withdrawal symptoms; the scores of non-smokers fell between those of abstinent and satiated smokers, more closely approximating those of the latter. By contrast, sadness ratings in response to negative clips were not affected by smoking status, indicating that the effect on happiness was not simply due to general emotional blunting. These results suggest that, for regular smokers, stimuli that are motivationally salient for the general population may elicit reduced positive affective responses during periods of abstinence.     

The GABAB receptor agonist baclofen prevents heroin-induced reinstatement of heroin-seeking behavior in rats

Opiate addiction is a chronic relapsing disorder characterized by high rates of relapse. The gamma-aminobutyric acid GABA(B) receptor agonist baclofen is known to affect the reinforcing effects of several drugs of abuse, including heroin, as well as to decrease cue-maintained responding for heroin, cocaine and nicotine and suppress alcohol deprivation effect in rats. Here we studied the effect of baclofen on the reinstatement of extinguished heroin-seeking behavior triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin (30 microg/kg per infusion) under a continuous reinforcement schedule. Following extinction, the effect of non-contingent non-reinforced primings with heroin, baclofen or heroin/baclofen combination on the resumption of responding was evaluated. Results indicate that heroin priming (0.25mg/kg) promptly reinitiated heroin-seeking behavior, an effect dose-dependently reduced by baclofen at doses (0.625 and 1.25mg/kg) not affecting responding per sè. Importantly, baclofen did not affect locomotion either alone or in combination with heroin, dispelling any doubt as to the eliciting of possible non-specific (motor) effects. The present results show that GABA(B) receptor activation may reduce the propensity to resume drug-induced heroin-seeking behavior thus offering a possible approach in maintaining opiate abstinence.