Effects of Ro 15-4513, alone or in combination with ethanol, Ro 15-1788, diazepam, and pentobarbital on instrumental behaviors of rats.
Intraperitoneally administered Ro 15-4513 and ethanol (ETOH), singly and in combination, were examined in rats. Leaping, climbing, bar-pressing, open-field (O-F) activity, as well as concentrations of ETOH in rebreathed air, were studied. Rats in the ETOH (1.2 g/kg) plus Ro 15-4513 (3 mg/kg) condition evinced a jumping performance significantly better than that of the ETOH singly-treated rats; the ETOH (1.2 g/kg) plus Ro 15-4513 (10 mg/kg) condition was intermediate to those of the ETOH and vehicle conditions. In the climbing and bar-pressing experiments, Ro 15-4513 did not attenuate the ETOH-induced impairments. Yet, ETOH improved performance of the Ro 15-4513 high dose (10 mg/kg) condition in the climbing situation. Additional findings were that a) intrinsic activity was noted with Ro 15-4513 in the climbing and bar-pressing situations, and b) the Ro 15-4513/ETOH combination in the O-F test resulted in reduced defecation (antagonism) and rearing activity similar to that of the ETOH-treated rats (lack of antagonism). Concentrations of ETOH in rebreathed air suggested no significant differences between the ETOH singly as compared to the ETOH plus Ro 15-4513 groups. Thus the antagonism of ETOH by Ro 15-4513 was dependent on the parameter examined. Additional experiments examined combinations of Ro 15-4513, Ro 15-1788, diazepam, and pentobarbital in the bar-pressing situation. Results were compatible with the view that Ro 15-4513 acts as a partial benzodiazepine inverse agonist.
Hiltunen
A J
AJ
University of Uppsala, Department of Clinical Psychology, Sweden.
Järbe
T U
TU
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001386:Azides; D001569:Benzodiazepines; D000431:Ethanol; D005442:Flumazenil; C042957:Ro 15-4513; D010424:Pentobarbital; D003975:Diazepam