: ,4, s' , '< .* ELSEVIER Neuroscience Letters 182 (1994) 247 250 NEUROSCIENC[ LETTERS Opposite effects of cholinergic agents and benzodiazepine receptor ligands in a passive avoidance task in rats Fran?oise Anglade a'*, Jean-Charles Bizot a, Robert H. Dodd b, Claude Baudoin c, Georges Chapouthier d aDGA/ETCA/CEB, BP 3, Vert-le-Petit 91710, France blCSN, CNRS, Gif-sur- Yvette 91198, France CLEEC, Universitk Paris-Nord, Villetaneuse 93430, France aLGNC, UFR Biomkdicale, Universitk Paris V, Paris 75006, France Received 16 June 1994; Revised version received 7 October 1994; Accepted 7 October 1994 Abstract Benzodiazepine (Bzd) agonist, diazepam (Dzp) and inverse agonist methyl fl-carboline-3-carboxylate (fl-CCM); acetylcholi- nesterase inhibitor, physostigmine(Physo) and muscarinic antagonist, scopolamine (Scopo), were investigated for their mnesic effect in a passive avoidance (PA) task in rats. Impairments were observed after Dzp- and/or Scopo-pretraining treatments. Physo was without effect but antagonized the Dzp-induced impairments, fl-CCM enhanced acquisition and antagonized the Scopo-induced impairing effect. All these drugs had no effect in posttraining administration. Key words." Memory; Cholinergic agent; Benzodiazepine; Passive avoidance; Rat Bzd treatment induces learning impairments which can be attributed to anterograde amnesic-like effects [19]. The Bzd receptor inverse agonist, fl-CCM, with anxio- genic and convulsant properties has been found to im- prove memory in rodents [5,11]. Cholinomimetic drugs, such as Physo, an acetylcholinesterase inhibitor, is known to facilitate learning in humans [18] but also to impair or improve learning in rats [3]. Mnesic deficits, attributed to a disruption of acquisition or consolida- tion, have been observed after muscarinic blockade by antagonists, such as Scopo [8]. Combined administration of Bzd and cholinergic agents has been less investigated on learning processes [9,12,17]. The purpose of the pres- ent study was to investigate the effects of these combined treatments in a one-trial PA task in rats. Each compound was administered alone (in pre- or posttraining) before investigating their combined action. *Corresponding author. Address: Centre d'l~tudes du Bouchet, Laboratoire de Pharmacologic du Comportement, Le Bouchet, BP 3, Vert-le-Petit 91710, France. 0304-3940/94/$7.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0304-3940(94)00800-0 Subjects were male Wistar rats (220-250 g; Janvier, France) and housed in standard conditions, with food and water ad libitum. The PA apparatus consisted of a lit compartment (LC) (50/40/34 cm) and a smaller dark compartment (DC) (28/26/24 cm). An 8-W bulb in the LC provided the only illumination during the experi- ments. In the DC, a grid floor was connected to a scram- bled shock distributor (Coulbourn Instruments). Access from the LC to the DC could be controlled through a guillotine door. Dzp 2, 4, 6 and 8 mg/kg (Roch6, France) was suspended in distilled water (dw) with a drop of acacia gum (Sigma, France). fl-CCM 0.3, 0.5, 1, 2 and 5 mg/kg (synthesized by one of us, R.H. Dodd) was dissolved in a 0.1 N HC1 solution and diluted in dw. Physo 0.125, 0.25 and 0.5 mg/kg (Sigma) and Scopo 0.1, 0.3, 0.5 and 1 mg/kg (Sigma) were dissolved in dw. Injec- tions were given i.p. in a volume of 1 ml/kg body weight. Control animals received the same volume of dw to which was added acacia gum or 0.1 N HC1 solution, depending on the experiment. Drugs were administered either 30 (Dzp), 20 (Scopo) or 15 min (fl-CCM, Physo) before the training session or just immediately after.