Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats.
BACKGROUND
There is controversy over whether exposure to stress precipitates relapse and/or increases alcohol (ethanol) intake. Our laboratory has demonstrated that repeated stress prior to withdrawal from a brief forced exposure to alcohol results in withdrawal-induced anxiety-like behavior. Because anxiety is often regarded as a precipitating factor in relapsing alcoholics, we decided to examine the consequences of stressing alcohol-preferring P rats on both voluntary alcohol drinking and withdrawal-induced anxiety.


METHODS
P rats were subjected to 3 cycles of 5 days of voluntary alcohol drinking and 2 days of deprivation. Restraint stress (60 min) was applied to some animals during the first and second deprivations/withdrawals (at 4 h). Drugs (flumazenil, buspirone, SB242,084, CP154,526, CRA1000, naloxone, haloperidol, olanzapine, naloxone, and haloperidol) were given to some rats 30 min prior to restraint stress.


RESULTS
Stressed, deprived P rats exhibited both a longer duration of elevated alcohol drinking and anxiety-like behavior in the social interaction test upon withdrawal after the third cycle of voluntary alcohol drinking. When given prior to each of the restraint stresses, the benzodiazepine receptor antagonist flumazenil (5 mg/kg), the corticotrophin releasing factor receptor antagonists CRA1000 (3 mg/kg) and CP154,526 (10 mg/kg), the serotonin 5-HT(1A) receptor partial agonist buspirone (0.6 mg/kg), and the mixed 5-HT(2C)/D2 receptor antagonist olanzapine were effective in reducing the increased duration of elevated alcohol drinking and the withdrawal-induced anxiety-like behavior. In contrast, while the opiate receptor antagonist naloxone (20 mg/kg), the 5-HT(2C) receptor antagonist SB242084 (3 mg/kg), and the dopamine receptor antagonist haloperidol (0.1 mg/kg) also reduced drinking, they did not significantly alter anxiety like behavior.


CONCLUSIONS
These results suggest that stress-induced facilitation of alcohol drinking and withdrawal-induced anxiety-like behavior in P rats may be closely but imperfectly linked.
Overstreet
David H
DH
Department of Psychiatry, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA. dhover@med.unc.edu
Knapp
Darin J
DJ
Breese
George R
GR
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D000077152:Olanzapine; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical / Q000009:adverse effects / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology*
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D014151:Anti-Anxiety Agents; D018492:Dopamine Antagonists; D018757:GABA Modulators; D007211:Indoles; D009292:Narcotic Antagonists; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; D009270:Naloxone; D000431:Ethanol; D005442:Flumazenil; D006220:Haloperidol; D000077152:Olanzapine; D002065:Buspirone