A microdialysis profile of dynorphin A(1-8) 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 endorphinergic and enkephalinergic activity, while very few studies have examined its effect on dynorphinergic systems. The aim of the present study was to investigate the effect of alcohol administration or a mechanical stressor on extracellular levels of dynorphin A(1-8) 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 1.5 microL/min in awake and freely moving animals and the dialysate was collected at 30-minute intervals. In one experiment, following a baseline period, rats were injected intraperitoneally with either physiological saline or 1 of 3 doses of alcohol, 0.8, 1.6, or 3.2 g ethanol/kg body weight. In a second experiment, following a baseline period, rats were applied a clothespin to the base of their tail for 20 minutes. The levels of dynorphin A(1-8) in the dialysate were analyzed with solid-phase radioimmunoassay.


RESULTS
Relative to saline-treated controls, an alcohol dose of 1.6 and 3.2 g/kg caused a transient increase in the extracellular levels of dynorphin A(1-8) in the first 30 minutes of alcohol administration. However, the effect resulting from the high 3.2 g/kg dose was far more pronounced and more significant than with the moderate dose. There was no effect of tail pinch on dynorphin A(1-8) levels in the nucleus accumbens.


CONCLUSIONS
In this experiment, a very high dose of alcohol was especially capable of stimulating dynorphin A(1-8) release in the nucleus accumbens. Dynorphin release in the accumbens has been previously associated with aversive stimuli and may thus reflect a system underlying the aversive properties of high-dose alcohol administration. However, the lack of effect of tail-pinch stress in the present study suggests that dynorphin A(1-8) is not released in response to all forms of stressful/aversive stimuli.
Marinelli
Peter W
PW
Department of Neurology and Neurosurgery, Douglas Hospital Research Centre and McGill University, Montréal, Québec, Canada.
Lam
Minh
M
Bai
Li
L
Quirion
Rémi
R
Gianoulakis
Christina
C
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013623:Tail
D010446:Peptide Fragments; D000431:Ethanol; D004399:Dynorphins; C026770:dynorphin (1-8)