Relapse to alcohol addiction after prolonged withdrawal periods is a major problem in the treatment of alcohol dependence in humans. One factor thought to trigger relapse is exposure to the environment in which alcohol was consumed. At a pre-clinical level it has been possible to study this effect in the reinstatement model, in which the environmental stimuli are represented by cues, like tones or lights. This model has also been pharmacologically validated with compounds that are used clinically for treating alcoholics: the non-selective opioid receptors antagonist naltrexone has proven to be effective in attenuation of alcohol reinstatement induced by discrete cues and by drug priming. Using the reinstatement model we evaluated the effect of the physical characteristics of the environment in which ethanol is consumed on reinstatement of ethanol-seeking behavior. Rats were trained to lever press for ethanol in one context, responding was then extinguished in a context that differed by visual, tactile and olfactory cues. During test for reinstatement animals were placed in the ethanol-paired context. The acute effect of naltrexone (0.3 mg/kg) has been examined injecting the animals 20 minutes prior to the reinstatement test. As compared to the extinction levels re-exposure to the alcohol-associated context significantly increased responses on the active lever. Pre-treatment with naltrexone significantly decreased responding at the active lever, but not the inactive, compared to the saline-treated subjects. These findings are in accordance with clinical reports, which find high rates of relapse when drug addicts return to their home environments. The effect of naltrexone on the context-induced reinstatement of ethanol self-administration, demonstrates the involvement of the endogenous opioid system in processes underlying relapse to ethanol, and is in accordance with clinical findings demonstrating its efficacy in the treatment of alcohol relapse in humans.
Context-induced reinstatement of ethanol self-administration: acute effect of naltrexone
BURATTINI, COSTANZA;AICARDI, GIORGIO;
2004
Abstract
Relapse to alcohol addiction after prolonged withdrawal periods is a major problem in the treatment of alcohol dependence in humans. One factor thought to trigger relapse is exposure to the environment in which alcohol was consumed. At a pre-clinical level it has been possible to study this effect in the reinstatement model, in which the environmental stimuli are represented by cues, like tones or lights. This model has also been pharmacologically validated with compounds that are used clinically for treating alcoholics: the non-selective opioid receptors antagonist naltrexone has proven to be effective in attenuation of alcohol reinstatement induced by discrete cues and by drug priming. Using the reinstatement model we evaluated the effect of the physical characteristics of the environment in which ethanol is consumed on reinstatement of ethanol-seeking behavior. Rats were trained to lever press for ethanol in one context, responding was then extinguished in a context that differed by visual, tactile and olfactory cues. During test for reinstatement animals were placed in the ethanol-paired context. The acute effect of naltrexone (0.3 mg/kg) has been examined injecting the animals 20 minutes prior to the reinstatement test. As compared to the extinction levels re-exposure to the alcohol-associated context significantly increased responses on the active lever. Pre-treatment with naltrexone significantly decreased responding at the active lever, but not the inactive, compared to the saline-treated subjects. These findings are in accordance with clinical reports, which find high rates of relapse when drug addicts return to their home environments. The effect of naltrexone on the context-induced reinstatement of ethanol self-administration, demonstrates the involvement of the endogenous opioid system in processes underlying relapse to ethanol, and is in accordance with clinical findings demonstrating its efficacy in the treatment of alcohol relapse in humans.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
