Pharmacological modulation of repeated ethanol withdrawal-induced anxiety-like behavior differs in alcohol-preferring P and Sprague-Dawley rats.
Previous work with Sprague-Dawley (SD) rats indicated that subjecting these rats to multiple episodes of ethanol diet could provoke anxiety-like responses. Because alcohol-preferring P rats have been reported to have neurochemical alterations in many systems shown to modulate anxiety-like responses, P rats were compared to SD rats. Rats were subjected to one or three cycles of 5 days' exposure to 4.5% or 7% ethanol diet to assess anxiety-like behavior. The social interaction test was conducted 5 h after ethanol was removed. Other groups of P and SD rats were injected with flumazenil (5 mg/kg), a benzodiazepine (BZD) receptor antagonist, CP-154,526 (10 mg/kg), CRF1 receptor antagonist, SB243,213, a 5-HT2C receptor inverse agonist, or vehicle during the 1st and 2nd withdrawals but not the third. After a single 5-day cycle of ethanol exposure, SD rats did not exhibit a change in social interaction, but P rats exhibited a decrease after exposure to the 7% ethanol. Both strains of rats exhibited anxiety-like behavior following three cycles of exposure to ethanol and the concentration of ethanol in the diet did not influence the response. It was confirmed that flumazenil, CP-154,523, and SB243,213 had prophylactic effects on anxiety-like behavior in the SD rats. Neither flumazenil nor SB243,213 was as effective in the P rats, while the CRF1 receptor antagonist completely counteracted the reduced social interaction in repeatedly withdrawn P rats. A small study showed that buspirone, a 5-HT1A agonist, also had prophylactic effects in P rats. These findings show that alcohol-preferring P rats exhibit anxiety-like behavior more readily following exposure to ethanol-containing diets and that this behavior is counteracted more readily by pretreatment with a CRF1 receptor antagonist than with BZD or 5-HT2C receptor antagonists.
Overstreet
David H
DH
Bowles Center for Alcohol Studies, Department of Psychiatry, 3009 Thurston-Bowles Bldg., CB #7178, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA. dhover@med.unc.edu
Knapp
Darin J
DJ
Breese
George R
GR
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D000431:Ethanol / Q000008:administration & dosage*; D005442:Flumazenil / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007398:Interpersonal Relations; D008297:Male; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology
D007211:Indoles; D011725:Pyridines; D000431:Ethanol; D005442:Flumazenil; C406343:SB 243213