Selective antagonism of acute ethanol-induced motor disturbances by centrally administered Ro 15-4513 in mice.
Results of the present investigation demonstrated that Ro 15-4513 when given ICV selectively antagonized ethanol-induced motor disturbances at doses that did not produce motor incoordination and lacked proconvulsant activity. Ro 15-4513 in 10-, 15-, and 22-ng doses antagonized, roughly in a dose-dependent manner, ethanol-induced motor incoordination. The 10-ng dose produced an optimal effect with nearly complete antagonism within 30 min postethanol. The higher, 15 and 22 ng, doses of Ro 15-4513 antagonized, as well as probably reversed, ethanol-induced motor incoordination. The stimulation and inhibition of spontaneous motor activity by 1 and 2 g/kg IP ethanol, respectively, were also selectively antagonized by Ro 15-4513. Neither an alteration in the latency and/or duration of pentylenetetrazol-induced convulsions nor an antagonism to sodium pentobarbital-induced motor incoordination and inhibition of spontaneous motor activity by Ro 15-4513 at dose levels that showed antiethanol effects were observed. Only the 150-ng dose of Ro 15-4513, which exhibited intrinsic activity as proconvulsant, attenuated sodium pentobarbital-induced motor incoordination. When given alone at doses higher than those used in motor coordination experiments, Ro 15-4513 markedly increased spontaneous motor activity dose dependently.
Dar
M S
MS
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
D000818:Animals; D001386:Azides / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D000431:Ethanol / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole; D011597:Psychomotor Performance / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D001386:Azides; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513; D010424:Pentobarbital; D010433:Pentylenetetrazole