Funded through a grant from the Natural Sciences and Engineering Research Council of Canada. P. Marinelli was supported by fellowships from the Centre for Addiction and Mental Health and the Ontario Mental Health Foundation.
A Microdialysis Profile of Met-Enkephalin Release in the Rat Nucleus Accumbens Following Alcohol Administration
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 29, Issue 10, pages 1821–1828, October 2005
How to Cite
Marinelli, P. W., Bai, L., Quirion, R. and Gianoulakis, C. (2005), A Microdialysis Profile of Met-Enkephalin Release in the Rat Nucleus Accumbens Following Alcohol Administration. Alcoholism: Clinical and Experimental Research, 29: 1821–1828. doi: 10.1097/01.alc.0000183008.62955.2e
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication February 1, 2005; accepted July 11, 2005.
Abstract: Background: Pharmacological studies have implicated the endogenous opioid system in mediating alcohol intake. Other evidence has shown that alcohol administration can influence opioid activity. In this regard, the majority of studies have concentrated on endorphinergic systems, whereas other opioid systems have been granted comparably less attention. This is the case despite some compelling evidence that has implicated enkephalinergic peptide systems, particularly Met-enkephalin, in mediating alcohol preference. The aim of the present study was to investigate the effect of alcohol administration on extracellular levels of Met-enkephalin in the rat nucleus accumbens—a brain region that plays a significant role in the processes underlying reinforcement and stress.
Methods: Male Sprague-Dawley rats were implanted with a microdialysis probe aimed at the shell region of the nucleus accumbens. Artificial cerebrospinal fluid was pumped at a rate of 1.75 μl/min in awake and freely moving rats and dialysates were collected at 30-minute intervals. After several baseline collections, rats were injected intraperitoneally with either physiological saline or one of four doses of alcohol: 0.8, 1.6, 2.4, or 3.2 g/kg ethanol body weight. The levels of Met-enkephalin in the dialysates were analyzed with solid-phase radioimmunoassay.
Results: Within the first 30 minutes of administration, an alcohol dose of 1.6 g/kg caused a significant and prolonged elevation in the extracellular levels of Met-enkephalin. Alcohol did not have a major effect on the release of Met-enkephalin at any other dose.
Conclusions: In this experiment, only a moderate dose of alcohol was capable of stimulating Met-enkephalin release in the nucleus accumbens. Enkephalins may modulate local neurotransmitter release by binding to presynaptic Δ-opioid receptors, or, they may inhibit effector cells by binding to postsynaptic Δ- or μ-opioid receptors. This may be one of multiple neurological mechanisms that modulate alcohol-drinking behavior.