The novel anticonvulsant loreclezole (R 72063) does not produce diazepam-like anterograde amnesia in a passive avoidance test in rats.
Rats were injected intraperitoneally with loreclezole (R 72063), diazepam, or scopolamine 60 min prior to acquisition of a passive avoidance task and tested 18 h later for retention of the learned (passive) behavior. The known impairment of performance produced by diazepam in this test is believed to be a model for the clinically observed diazepam-induced anterograde amnesia in humans. We report in this study that (1) consistent with the literature, pretreatment with diazepam (2.0-16.0 mg/kg i.p.) or scopolamine (3.0 mg/kg i.p.) produced impairment in passive avoidance performance of rats (anterograde amnesia), but (2) pretreatment with loreclezole (R 72063) (2.0-80.0 mg/kg i.p.) did not impair the acquisition, retention, or the retrieval (tested 18 h later) of passive avoidance behavior by rats at any dose. The results suggest that the anticonvulsant activity of loreclezole is mediated by a mechanism distinct from the one coupled to diazepam-like disruption of cognitive functions involved in the acquisition or posttraining information processing of passive avoidance behavior.
Raffa
R B
RB
Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477-0776.
Vaught
J L
JL
Setler
P E
PE
D000647:Amnesia / Q000139:chemically induced*; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001362:Avoidance Learning / Q000187:drug effects*; D003975:Diazepam / Q000633:toxicity*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000633:toxicity; D014230:Triazoles / Q000633:toxicity*
D000927:Anticonvulsants; D014230:Triazoles; C066440:loreclezole; D012601:Scopolamine; D003975:Diazepam