A microdialysis profile of Met-enkephalin release in the rat nucleus accumbens following alcohol administration.
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 mul/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 Delta-opioid receptors, or, they may inhibit effector cells by binding to postsynaptic Delta- or mu-opioid receptors. This may be one of multiple neurological mechanisms that modulate alcohol-drinking behavior.
Marinelli
Peter W
PW
Biobehavioural Pharmacology Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Bai
Li
L
Quirion
Rémi
R
Gianoulakis
Christina
C
D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D000431:Ethanol; D004744:Enkephalin, Methionine