Ethanol self-administration in freely feeding and drinking rats: effects of Ro15-4513 alone, and in combination with Ro15-1788 (flumazenil).
Recent work in our laboratory demonstrated that Ro15-4513, a partial inverse benzodiazepine (BDZ) agonist, decreases ethanol (ETOH) self-administration in rodents under fluid deprivation conditions. The present study further examined the effects of Ro15-4513 (2.5 and 5.0 mg/kg) alone and in combination with Ro15-1788, (flumazenil) (8.0 and 16.0 mg/kg), a BDZ receptor antagonist on ETOH self-administration in freely feeding and drinking rats. Animals were trained to consume ETOH (11% v/v) using a limited access procedure. Measurements were taken at 10- and 60-min intervals. Ro15-4513 (2.5 and 5.0 mg/kg) markedly attenuated ETOH consumption at both intervals. The antagonistic actions of Ro15-4513 were completely blocked by the higher dose of flumazenil at both intervals; the lower dose failed to antagonize the Ro15-4513-induced reduction of ETOH intake. When flumazenil was given alone, both doses reduced ETOH self-administration at 60 min; although the magnitude of the antagonism was comparable to that of Ro15-4513 only with the highest does of flumazenil (16.0 mg/kg). Neither Ro15-4513 nor flumazenil alone or in combination significantly altered water intake at any of the tested doses. Rats pretreated with Ro15-4513 showed a substantial reduction in blood ethanol concentration (BEC) compared with the Tween-80 vehicle condition at the 10-min interval. However, the BEC of animals given Ro15-4513 in combination with flumazenil were similar to rats given Tween-80 vehicle. The present study extends our previous research by demonstrating that Ro15-4513 and flumazenil attenuate ETOH self-administration in non-food or water deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS)
June
H L
HL
Department of Psychology, Howard University, Washington, DC 20059.
Hughes
R W
RW
Spurlock
H L
HL
Lewis
M J
MJ
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood; D005442:Flumazenil / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology
D001386:Azides; D058785:GABA-A Receptor Agonists; D001569:Benzodiazepines; D000431:Ethanol; D005442:Flumazenil; C042957:Ro 15-4513