Dissociation between opioid and CRF1 antagonist sensitive drinking in Sardinian alcohol-preferring rats.
BACKGROUND
The role of positive vs negative ethanol reinforcement in ethanol intake of Sardinian alcohol-preferring (sP) rats is unclear.


OBJECTIVE
To test the hypothesis that spontaneous ethanol self-administration of sP rats was sensitive to the opioid receptor antagonist naltrexone, whereas withdrawal-induced, but not spontaneous, ethanol self-administration would be sensitive to corticotropin-releasing factor(1) (CRF(1)) antagonists, implicating differential roles for positive and negative reinforcement, respectively.


METHODS
Male sP rats operantly (FR1, 30 min/day) self-administered ethanol (10% v/v) until responding stabilized. One group (n=11) was made ethanol dependent through intermittent ethanol vapor exposure. Both nondependent (n = 10) and dependent rats received the CRF(1) antagonist LWH-63 (5, 10, and 20 mg/kg, s.c.). Separate nondependent sP rats (n = 10) received the opioid antagonist naltrexone (16, 50, 150, and 450 microg/kg, s.c.). Finally, CRF(1) antagonists (MJL-1-109-2, LWH-63, and R121919) were studied for their actions on home-cage ethanol drinking in nondependent sP rats (n = 6-8/group) under continuous, limited-access, or stressed conditions.


RESULTS
Naltrexone potently reduced ethanol self-administration in nondependent sP rats. LWH-63 reduced heightened ethanol self-administration of vapor-sensitive, dependent sP rats. CRF(1) antagonists did not reduce ethanol intake in nondependent sP rats. R121919 (10 mg/kg, s.c.) retained antistress activity in sP rats, blunting novelty stress-induced suppression of ethanol intake.


CONCLUSIONS
Spontaneous ethanol self-administration of sP rats was opioid dependent with CRF(1) receptors implicated in withdrawal-induced drinking. Opioid and CRF(1) receptors play different roles in ethanol reinforcement and perhaps the ethanol addiction cycle. Such distinctions may apply to subtypes of alcoholic patients who differ in their motivation to drink and ultimately treatment response.
Sabino
Valentina
V
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA. vsabino@sripps.edu
Cottone
Pietro
P
Koob
George F
GF
Steardo
Luca
L
Lee
Mei J
MJ
Rice
Kenner C
KC
Zorrilla
Eric P
EP
D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology*; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology; D002491:Central Nervous System Agents / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D014227:Triazines / Q000494:pharmacology; D000099052:CRF Receptor, Type 1
D002491:Central Nervous System Agents; C476980:MJL 1-109-2; D009292:Narcotic Antagonists; D011743:Pyrimidines; D011758:Pyrroles; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D014227:Triazines; C103016:antalarmin; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D009271:Naltrexone