Tolerance and Sensitization to Chronic Escalating Dose Heroin Following Extended Withdrawal in Fischer Rats: Possible Role of Mu-Opioid Receptors.
Tolerance and sensitization to chronic escalating dose heroin following extended withdrawal in Fischer rats: possible role of mu-opioid receptors.
Filed under: Addiction Rehab
Psychopharmacology (Berl). 2012 Jul 25;
Seip-Cammack KM, Reed B, Zhang Y, Ho A, Kreek MJ
RATIONALE/OBJECTIVES: Heroin addiction is characterized by recurrent cycles of drug use, abstinence, and relapse. It is likely that neurobiological changes during chronic heroin exposure persist across withdrawal and impact behavioral responses to re-exposure. We hypothesized that, after extended withdrawal, heroin-withdrawn rats would express behavioral tolerance and/or sensitization in response to heroin re-exposure and that these responses might be associated with altered mu-opioid receptor (MOPr) activity. METHODS: Male Fischer rats were exposed chronically to escalating doses of heroin (7.5-75 mg/kg/day), experienced acute spontaneous withdrawal and extended (10-day) abstinence, and were re-exposed chronically to heroin. Homecage behaviors and locomotor activity in response to heroin, as well as somatic withdrawal signs, were recorded. Separate groups of rats were sacrificed after extended abstinence and MOPr expression and G-protein coupling were analyzed using [(3)H]DAMGO and [(35)S]GTP?S assays. RESULTS: The depth of behavioral stupor was lower during the initial days of heroin re-exposure compared to the initial days of the first exposure period. Behavioral responses (e.g., stereotypy) and locomotion were elevated in response to heroin re-exposure at low doses. Rats conditioned for heroin place preference during the chronic re-exposure period expressed heroin preference during acute withdrawal; this preference was stronger than rats conditioned during chronic heroin exposure that followed chronic saline and injection-free periods. Extended withdrawal was associated with increased MOPr expression in the caudate-putamen and frontal and cingulate cortices. No changes in G-protein coupling were identified. CONCLUSIONS: Aspects of tolerance/sensitization to heroin are present even after extended abstinence and may be associated with altered MOPr density.
HubMed – addiction
Associative blocking to reward-predicting cues is attenuated in ketamine users but can be modulated by images associated with drug use.
Filed under: Addiction Rehab
Psychopharmacology (Berl). 2012 Jul 25;
Freeman TP, Morgan CJ, Pepper F, Howes OD, Stone JM, Curran HV
RATIONALE: Blocking is an associative learning process that is attenuated in schizophrenia, can be modulated by cue salience and is accompanied by changes in selective attention. Repeated exposure to ketamine can model aspects of schizophrenia, and frequent users selectively attend to images of the drug. OBJECTIVES: This study aimed to establish whether (1) ketamine users show attenuated blocking to reward-predicting cues and (2) drug cues can modulate blocking and cause overshadowing of neutral cues that are equally predictive of reward in these individuals. METHODS: Ketamine users (n?=?18) and polydrug controls (n?=?16) were assessed on the Drug Cue Reward Prediction Error Task, which indexes blocking and overshadowing to neutral and drug-related cues following Pavlovian reward conditioning. Schizotypy, depression, drug history and ketamine dependence were also assessed. RESULTS: Compared to controls, ketamine users showed elevated delusional, schizotypal and depressive symptoms, and a reduction in blocking as evidenced by higher accuracy to blocked cues. Drug-related cues were resistant to blocking and seen as more important for earning money by ketamine users compared to controls. Both groups showed overshadowing of neutral cues by drug cues, and ketamine users gave both of these cues higher importance ratings than controls. CONCLUSIONS: These findings provide the first evidence that (1) glutamatergic perturbation is linked to a reduction in blocking and (2) blocking can be modulated by the presence of drug-related cues. The ability of drug cues to bias selective learning about ‘alternative rewards’ has implications for contingency management based addiction treatments.
HubMed – addiction
Do Client Attributes Moderate the Effectiveness of a Group Cognitive Behavioral Therapy for Depression in Addiction Treatment?
Filed under: Addiction Rehab
J Behav Health Serv Res. 2012 Jul 25;
Hunter SB, Paddock SM, Zhou A, Watkins KE, Hepner KA
The study goal was to determine whether client attributes were associated with outcomes from group cognitive behavioral therapy for depression (GCBT-D) as delivered in community-based addiction treatment settings. Data from 299 depressed residential clients assigned to receive either usual care (N?=?159) or usual care plus GCBT-D (N?=?140) were examined. Potential moderators included gender, race/ethnicity, education, referral status, and problem substance use. Study outcomes at 6 months post-baseline included changes in depressive symptoms, mental health functioning, negative consequences from substance use, and percentage of days abstinent. Initial examination indicated that non-Hispanic Whites had significantly better outcomes than other racial/ethnic groups on two of the four outcomes. After correcting for multiple testing, none of the examined client attributes moderated the treatment effect. GCBT-D appears effective; however, the magnitude and consistency of treatment effects indicate that it may be less helpful among members of racial/ethnic minority groups and is worthy of future study.
HubMed – addiction
Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice.
Filed under: Addiction Rehab
Neuropsychopharmacology. 2012 Jul 25;
Hilario MR, Turner JR, Blendy JA
Tobacco dependence is an addiction with high rates of relapse, resulting in multiple quit attempts in individuals who are trying to stop smoking. How these multiple cycles of smoking and withdrawal contribute to nicotine dependence, long-term alterations in brain reward systems, and nicotine receptor regulation is unknown. Therefore, to evaluate how multiple exposures of nicotine and withdrawal periods modulate rewarding properties of nicotine, we used intracranial self-stimulation to measure alterations in the threshold of brain stimulation reward. In addition, we employed the conditioned place preference (CPP) paradigm to evaluate positive context conditioning following each withdrawal period and measured levels of neuronal nicotinic receptors in cortex, striatum, and hippocampus. We found that repeated nicotine exposure and withdrawal enhanced brain stimulation reward and reward sensitivity to acute injections of nicotine. This increased reward was reflected by enhanced CPP to nicotine. Chronic nicotine is known to up-regulate nAChRs (nicotinic acetylcholine receptors) and we found that this up-regulation was maintained for up to 8 days of withdrawal in the striatum and in the hippocampus, but not in the cortex, of animals exposed to multiple nicotine exposure and withdrawal periods. These results demonstrate that repeated exposures to nicotine, followed by withdrawal, induce a persistent increase in both brain reward function and sensitivity to the hedonic value of nicotine and long-lasting up-regulation of neuronal nicotinic receptors. Together, these data suggest that a continuing increase in brain reward function and enhanced sensitivity to nicotine reward following repeated withdrawal periods may be one reason why smokers relapse frequently.Neuropsychopharmacology advance online publication, 25 July 2012; doi:10.1038/npp.2012.130.
HubMed – addiction
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