Effects of benzodiazepines on passive avoidance response and latent learning in mice: Relationship to benzodiazepine receptors and the cholinergic neuronal system

Toshitaka Nabeshima, K. Tohyama, K. Ichihara, T. Kameyama

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The effects of benzodiazepines on learning and memory were investigated, using passive avoidance and latent learning tasks, with particular attention being paid to the possible involvement of benzodiazepine receptors and the cholinergic neuronal system. Benzodiazepines such as diazepam, nitrazepam and chlordiazepoxide (CDP) impaired the passive avoidance response when administered before training, but not when administered immediately after training or before the retention test. CDP also impaired latent learning in the water finding task. State-dependent learning was not observed with CDP at the dose used. A benzodiazepine inverse agonist, Ro 15-4513, and a benzodiazepine antagonist, Ro 15-1788, completely and partially reversed, respectively, the disruptive effects of CDP on learning and memory at the doses which did not enhance learning and memory. The disruptive effects of CDP on learning and memory were partially antagonized by a choline esterase inhibitor, physostigmine, and by a blocker for muscarinic acetylcholine receptors, scopolamine, at the doses which increase acetylcholine release. These results suggest that benzodiazepines induce disruptive effects on learning and memory through benzodiazepine receptors, and that benzodiazepine-induced impairment of learning and memory is, at least in part, the result of the dysfunction of the cholinergic neuronal system.

Original languageEnglish
Pages (from-to)789-794
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume255
Issue number2
Publication statusPublished - 01-01-1990
Externally publishedYes

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GABA-A Receptors
Benzodiazepines
Cholinergic Agents
Chlordiazepoxide
Learning
Nitrazepam
Avoidance Learning
Flumazenil
Physostigmine
Scopolamine Hydrobromide
Muscarinic Receptors
Esterases
Diazepam
Choline
Acetylcholine
Water

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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abstract = "The effects of benzodiazepines on learning and memory were investigated, using passive avoidance and latent learning tasks, with particular attention being paid to the possible involvement of benzodiazepine receptors and the cholinergic neuronal system. Benzodiazepines such as diazepam, nitrazepam and chlordiazepoxide (CDP) impaired the passive avoidance response when administered before training, but not when administered immediately after training or before the retention test. CDP also impaired latent learning in the water finding task. State-dependent learning was not observed with CDP at the dose used. A benzodiazepine inverse agonist, Ro 15-4513, and a benzodiazepine antagonist, Ro 15-1788, completely and partially reversed, respectively, the disruptive effects of CDP on learning and memory at the doses which did not enhance learning and memory. The disruptive effects of CDP on learning and memory were partially antagonized by a choline esterase inhibitor, physostigmine, and by a blocker for muscarinic acetylcholine receptors, scopolamine, at the doses which increase acetylcholine release. These results suggest that benzodiazepines induce disruptive effects on learning and memory through benzodiazepine receptors, and that benzodiazepine-induced impairment of learning and memory is, at least in part, the result of the dysfunction of the cholinergic neuronal system.",
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