RO5-4864, a ligand for benzodiazepine micromolar and peripheral binding sites: antagonism and enhancement of behavioural effects.
RO5-4864, a ligand for both the peripheral and for the central nervous system micromolar benzodiazepine binding sites, was investigated in the holeboard, alone and in combination with several other drugs. RO5-4864 alone caused a marked reduction in rears and motor activity and reduced head-dipping when objects were placed under the holes. All these reductions were enhanced by picrotoxin (2 and 4 mg/kg) and by CGS 8216 (3 mg/kg). RO15-1788 (10 mg/kg) reversed the reduction in rears and PK11195 (30 mg/kg), a putative antagonist for the peripheral binding site, reversed the reduction in head-dipping. The results are discussed in terms of the various benzodiazepine binding sites and possible non-specific drug effects.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004347:Drug Interactions; D005442:Flumazenil; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A
D001570:Benzodiazepinones; D005442:Flumazenil; D010672:Phenytoin; D010852:Picrotoxin; D011720:Pyrazoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one