Central administration of an opiate antagonist decreases oral ethanol self-administration in rats

Background: Opioid peptides have been implicated in various behavioral acti ons of alcohol, including its reinforcing effects; however, the role of spe cific brain sites for these actions remains to be explored. The present stu dy examined the effects of intracerebroventricular (ICV) or intracerebral i njections of an opiate antagonist (methylnaloxonium) on ethanol self-admini stration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effect s of drugs of abuse. Methods: Male Wistar rats were trained in a limited-access paradigm (30 min /day) to respond for ethanol (10% w/v) or water in a two-lever free-choice condition using a saccharin fading procedure. After the establishment of st able baseline responding for ethanol, animals were implanted stereotasicall y with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperativ e recovery of stable baseline responding, the rats were tested 15 min after ICV or intracerebral microinjections of methylnaloxonium (0-2000 ng). Results: Injections of methylnaloxonium into the amygdala significantly red uced responding for ethanol at doses of 250-500 ng. Injections of methylnal oxonium into the nucleus accumbens significantly reduced responding for eth anol at doses of 500-1000 ng, whereas higher doses were needed ICV. Conclusions: These results provide evidence that opioid receptors located i n the amygdala and nucleus accumbens may be involved in the regulation of e thanol self-administration.