title: Double dissociation between the effects of muscarinic antagonists and benzodiazepine receptor agonists on the acquisition and retention of passive avoidance.
abstract: Both muscarinic antagonists, such as scopolamine, and benzodiazepine receptor (BZR) agonists, such as diazepam, produce a reliable impairment in the performance of one trial passive avoidance. Such deficits are frequently interpreted as drug-induced amnesia. However, these deficits could also result from a learning impairment. The present experiments compared the effects of two BZR agonists, lorazepam (0, 0.125, 0.25, and 0.375 mg/kg, IP) and diazepam (0, 0.78, 1.56, and 3.13 mg/kg, IP) with the effects of two muscarinic antagonists, scopolamine (0, 0.6, 0.8 and 1.0 mg/kg, SC) and atropine (0, 15, 30 and 60 mg/kg, IP) on a multiple trial passive avoidance task. In this procedure, the rats were trained with a 5-min inter-trial interval until a learning criterion was achieved. Retention was assessed 24 h later. This enabled the effects of the drugs on the acquisition and the retention of a passive avoidance response to be dissociated. Both atropine and scopolamine produced a marked impairment in the acquisition of the passive avoidance response, but did not impair retention. In contrast, diazepam and lorazepam did not alter the acquisition of a passive avoidance response, but did produce a dose-dependent impairment of retention. These results therefore demonstrate a double dissociation between the effects of muscarinic antagonists and BZR agonists on the acquisition and retention of passive avoidance.
authors.affiliation: Department of Neuropsychopharmacology, Research Laboratories of Schering AG, Berlin, Germany.
authors.forename: B J
authors.initials: BJ
authors.lastname: Cole
authors.forename: G H
authors.initials: GH
authors.lastname: Jones
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D008140:Lorazepam / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D058785:GABA-A Receptor Agonists; D018727:Muscarinic Antagonists; D001285:Atropine; D012601:Scopolamine; D008140:Lorazepam; D003975:Diazepam