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.
Similar content being viewed by others
References
Beatty WW, Butters N, Janowsky DS (1986) Patterns of memory failure after scopolamine treatment: Implications for cholinergic hypotheses of dementia. Behav Neural Biol 45:196–211
Berger BD, Stein L (1969) An analysis of the learning deficits produced by scopolamine. Psychopharmacologia 14:271–283
Bouton ME, Kenney FA, Rosengard C (1990) State-dependent fear extinction with two benzodiazepine tranquilizers. Behav Neurosci 104:44–55
Broekkamp CL, Le Pichon M, Lloyd KG (1984) The comparative effects of benzodiazepines, progabide and PK 9084 on acquisition of passive avoidance in mice. Psychopharmacology 83:122–125
Chiappetta L, Jarvik ME (1969) Comparison of learning impairment and activity depression produced by two classes of cholinergic blocking agents. Arch Int Pharmacodyn Ther 179:161–166
Chopin P, Briley M (1992) Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia. Psychopharmacology 106:26–30
Colpaert FC (1990) Amnestic trace locked into the benzodiazepine state of memory. Psychopharmacology 102:28–36
Curran HV, Schiwy W, Lader M (1987) Differential amnestic properties of benzodiazepines: a dose response comparison of two drugs with similar elimination half lives. Psychopharmacology 92:358–364
Decker MW, Tran T, McGaugh JL (1990) A comparison of the effects of scopolamine and diazepam on acquisition and retention of inhibitory avoidance in mice. Psychopharmacology 100:515–521
Dilts SL, Berry CA (1967) Effects of cholinergic drugs on passive avoidance in the mouse. J Pharmacol Exp Ther 158:279–285
Elrod K, Buccafusco JJ (1988) An evaluation of the mechanism of scopolamine-induced impairments in two passive avoidance protocols. Pharmacol Biochem Behav 29:15–21
Gamzu ER (1988) Animal model studies of benzodiazepine-induced amnesia. Psychopharmacol Ser 6:218–229
Glick SD, Zimmerberg B (1972) Amnestic effects of scopolamine. Behav Biol 7:245–254
Lopez CM, Govoni S, Battaini F, Bergamaschi S, Longoni A, Giaroni C, Trabucchi M, (1991) Effects of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamineinduced amnesia and brain acetylcholine. Pharmacol Biochem Behav 39:835–840
Miczek KA (1973) Effects of scopolamine, amphetamine and chlordiazepoxide on punishment. Psychopharmacologia 28:373–389
Nabeshima T, Tohyama K, Ichihara K, Kameyama T (1990) Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and cholinergic system. J Pharmacol Exp Ther 255:789–794
Oishi H, Iwahara S, Yang K-M, Yogi A (1972) Effects of chlordiazepoxide on passive avoidance responses in rats. Psychopharmacologia 23:373–385
Patel JB, Ciofalo VB, Iorio LC (1979) Benzodiazepine blockade of passive-avoidance task in mice: a state dependent phenomenon. Psychopharmacology 61:25–28
Rush DK (1986) Reversal of scopolamine induced amnesia of passive avoidance by pre- and post-training naloxone. Psychopharmacology 89:296–300
Rush DK (1988) Scopolamine amnesia of passive avoidance: a deficit in information acquisition. Behav Neural Biol 50:255–274
Rush DK, Streit K (1992) Memory modulation with peripherally acting cholinergic drugs. Psychopharmacology 106:375–382
Sanger DJ, Joly D (1985) Anxiolytic drugs and the acquisition of conditioned fear in mice. Psychopharmacology 85:284–288
Sepinwall J, Grodsky FS, Cook L (1978) Conflict behavior in the squirrel monkey: effects of chlordiazepoxide, diazepam and N-desmethydiazepam. J Pharmacol Exp Ther 204:88–102
Smith RF (1978) Scopolamine does not alter footshock sensitivity in the rat. Pharmacol Biochem Behav 8:31–34
Yamamoto M, Ooyama M, Ozawa Y, Okada M, Tada S, Yamaguchi T, Endo H (1993) Effects of indeloxazine hydrochloride, a cerebral activator, on passive avoidance learning impaired by disruption of cholinergic transmission in rats. Neuropharmacology 32:695–701
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cole, B.J., Jones, G.H. Double dissociation between the effects of muscarinic antagonists and benzodiazepine receptor agonists on the acquisition and retention of passive avoidance. Psychopharmacology 118, 37–41 (1995). https://doi.org/10.1007/BF02245247
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245247