This study was supported in part by the National Institute on Alcohol Abuse and Alcoholism Grants AA08459, AA06420, andAA07456 (G.F.K.) and Grant F32 AA05403 (C.J.H.).
Central Administration of an Opiate Antagonist Decreases Oral Ethanol Self-Administration in Rats
Article first published online: 31 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 23, Issue 9, pages 1468–1476, September 1999
How to Cite
Heyser, C. J., Roberts, A. J., Schulteis, G. and Koob, G. F. (1999), Central Administration of an Opiate Antagonist Decreases Oral Ethanol Self-Administration in Rats. Alcoholism: Clinical and Experimental Research, 23: 1468–1476. doi: 10.1111/j.1530-0277.1999.tb04669.x
- Issue published online: 31 MAY 2006
- Article first published online: 31 MAY 2006
- Received for publication January 5, 1999; accepted June 14, 1999.
- Nucleus Accumbens;
Background: Opioid peptides have been implicated in various behavioral actions of alcohol, including its reinforcing effects; however, the role of specific brain sites for these actions remains to be explored. The present study examined the effects of intracerebroventricular (ICV) or intracerebral injections of an opiate antagonist (methylnaloxonium) on ethanol self-administration. The nucleus accumbens and amygdala were selected as intracerebral sites because these regions have been implicated in the reinforcing effects 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 stable baseline responding for ethanol, animals were implanted stereotaxically with a guide cannula above the lateral ventricle or with bilateral guide cannulae either above the nucleus accumbens or amygdala. After postoperative 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 reduced responding for ethanol at doses of 250–500 ng. Injections of methylnaloxonium into the nucleus accumbens significantly reduced responding for ethanol at doses of 500–1000 ng, whereas higher doses were needed ICV.
Conclusions: These results provide evidence that opioid receptors located in the amygdala and nucleus accumbens may be involved in the regulation of ethanol self-administration.