Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats.
BACKGROUND
The role of the dynorphin/kappa-opioid receptor system in ethanol reinforcement is unclear.


OBJECTIVE
Examination of the effects of the highly selective kappa-opioid receptor agonist CI-977 (enadoline) and of the long-acting selective kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) on relapse-like drinking measured by the alcohol deprivation effect (ADE) in long-term ethanol-experienced rats.


METHODS
Rats were either implanted with mini-osmotic pumps delivering 0 or 0.01 mg/kg per h CI-977 or received two injections (12 h apart) of nor-BNI (0 or 5 mg/kg i.p.) before representation of alcohol after 2 weeks of alcohol deprivation in a four-bottle home cage drinking paradigm. In a second experiment, long-term ethanol-experienced rats trained in an operant ethanol self-administration paradigm received either acute CI-977 treatment (0, 0.003-0.1 mg/kg i.p.) or two injections (12 h apart) of nor-BNI (0 or 5 mg/kg i.p.) before a 23-h session.


RESULTS
Chronic CI-977 potentiated ethanol intake and preference during the ADE. Acute CI-977 dose-dependently reduced total lever pressing activity demonstrating an unspecific sedative effect, except for the lowest dose (0.003 mg/kg), which selectively increased lever pressing for ethanol during basal drinking. Nor-BNI did not affect relapse-like drinking at all.


CONCLUSIONS
Stimulation of kappa-opioid receptors can increase ethanol intake, at least in long-term ethanol-experienced rats. Since kappa-opioid receptor agonists have aversive motivational consequences, increased ethanol drinking might be an attempt to counteract the aversive effects of this treatment. On the other hand, the nor-BNI experiments indicate that endogenous kappa-opioid receptor stimulation does not seem to be involved in relapse-like drinking after protracted abstinence.
Hölter
S M
SM
Max Planck Institute of Psychiatry, Kraepelinstrasse 2, 80804 Munich, Germany. hoelter@mpipsykl.mpg.de
Henniger
M S
MS
Lipkowski
A W
AW
Spanagel
R
R
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012008:Recurrence; D012646:Self Administration
D001572:Benzofurans; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; C067110:enadoline