Ethanol and Ro 15-4513: behaviour maintained by operant procedures (DRL-72s and PTZ-drug discrimination) in rats.
The proposed amethystic imidazobenzodiazepine Ro 15-4513 and ethanol (ETOH) were examined in rats using two operant procedures, differential reinforcement of low rates of responding (DRL), and drug discrimination learning (DDL). In the first bar-pressing responses occurring 72 s or longer after the last reinforcement were rewarded; responses occurring earlier reset the time schedule. In the latter, animals were trained to discriminate between the effects of the analeptic pentylenetetrazole (PTZ) and the non-drug condition; the schedule of reinforcement was FR-10. Water was the reinforcer. A dose of 1000 mg/kg ETOH decreased the rate of bar pressing in the DRL experiment; doses of 300 and 560 mg/kg ETOH did not. The decrease was not attenuated by Ro 15-4513. No significant deviations from baseline responding occurred with Ro 15-4513 (1, 3 10 mg/kg). The number of reinforcements increased significantly after ETOH (1000 mg/kg), but not after Ro 15-4513. Combinations of the two agents produced increases in the number of reinforcements. Changes in DRL behaviour induced by diazepam (1 and 10 mg/kg) were normalized by 3 mg/kg Ro 15-4513. In DDL, Ro 15-4513 (10 mg/kg) substituted for PTZ; ETOH did not. Diazepam and Ro 15-1788 attenuated the response generalization from Ro 15-4513 to PTZ; ETOH did not. There was a dose-related increase in the time to complete the DDL tests after ETOH treatment; addition of Ro 15-4513 increased the time further. In conclusion, antagonism between Ro 15-4513 and ETOH did not occur in the present studies; data are furthermore consistent with the view that Ro 15-4513 acts as a partial inverse benzodiazepine agonist.
Järbe
T U
TU
University of Uppsala, Department of Psychology, Sweden.
Hiltunen
A J
AJ
D000818:Animals; D001386:Azides / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D010433:Pentylenetetrazole / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule
D001386:Azides; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513; D003975:Diazepam; D010433:Pentylenetetrazole