Attenuation of the discriminative stimulus effects of ethanol by the benzodiazepine partial inverse agonist Ro 15-4513.
The aim of the present study was to investigate whether ethanol training affects the ability of Ro 15-4513 to block the discriminative stimulus effects of ethanol dose differentially. Three different groups of rats were trained to discriminate 1.0 g/kg ethanol (n = 8), 1.5 g/kg ethanol (n = 7) or 2.0 g/kg ethanol (n = 8) from water in a two-lever, food-reinforced procedure. Ethanol and water were administered by gavage 20 min before the onset of the session. When the discrimination performance was stable, rats were pretreated with Ro 15-4513 (1-17 mg/kg; i.p.) 5 min before the administration of ethanol. Ro 15-4513 attenuated the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol but not 2.0 g/kg ethanol in each of the ethanol training groups. Overall, blockade of the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol by 5.6 mg/kg Ro 15-4513 occurred without significantly altering response rates or blood ethanol concentrations. A decrease in blood ethanol concentration was, however, found with 17 mg/kg Ro 15-4513 in combination with 2.0 g/kg ethanol. These results suggest that the benzodiazepine partial inverse agonist, Ro 15-4513, can attenuate the discriminative stimulus effects associated with low to moderate doses of ethanol (1.0-1.5 g/kg).
Gatto
G J
GJ
Department of Physiology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Grant
K A
KA
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051381:Rats
D001386:Azides; D002492:Central Nervous System Depressants; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513