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Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil.
Neuropharmacology. 1992 Mar; 31(3):299-306.N

Abstract

Synthetic benzodiazepines produce an anterograde amnesia, which can be reversed by selective benzodiazepine antagonists or inverse agonists. It has therefore been suggested that the memory-enhancing effects of the antagonists are due to antagonism of an endogenous "benzodiazepine-like" endocoid. If the memory-enhancing effects of the benzodiazepine antagonists are determined predominantly by the antagonism of such endogenous benzodiazepine-ligands, then it could be hypothesized that administration of an inverse agonist, which produces effects functionally opposite to those of benzodiazepine agonists, may also mimic the effects of benzodiazepine antagonists but not produce effects greater than those of the pure antagonists. The purpose of the present study was therefore to investigate the memory-enhancing effects of the benzodiazepine inverse agonist, ethyl-8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate (Ro 15-4513) in young HSD:(ICR)BR mice and to compare these effects with those of the benzodiazepine antagonist, flumazenil. Pretraining injections of flumazenil and Ro 15-4513 (2.5 and 10.0 mg/kg) enhanced equally, both the acquisition and the retention of a task for 1 week requiring mice to discriminate the correct arm of a T-maze, to avoid a mild electric shock. Pretreatment with Ro 15-4513 also dose-dependently protected the animals from experimental amnesia, induced by the cholinergic receptor antagonist, scopolamine in a second model of memory, in which mice were required to passively avoid a dark chamber after shock. In contrast, Ro 15-4513, injected prior to daily active avoidance sessions, failed to significantly improve either the acquisition or retention performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1630596

Citation

Prather, P L., et al. "Learning and Memory-enhancing Effects of Ro 15-4513: a Comparison With Flumazenil." Neuropharmacology, vol. 31, no. 3, 1992, pp. 299-306.
Prather PL, Forster MJ, Lal H. Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil. Neuropharmacology. 1992;31(3):299-306.
Prather, P. L., Forster, M. J., & Lal, H. (1992). Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil. Neuropharmacology, 31(3), 299-306.
Prather PL, Forster MJ, Lal H. Learning and Memory-enhancing Effects of Ro 15-4513: a Comparison With Flumazenil. Neuropharmacology. 1992;31(3):299-306. PubMed PMID: 1630596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Learning and memory-enhancing effects of Ro 15-4513: a comparison with flumazenil. AU - Prather,P L, AU - Forster,M J, AU - Lal,H, PY - 1992/3/1/pubmed PY - 1992/3/1/medline PY - 1992/3/1/entrez SP - 299 EP - 306 JF - Neuropharmacology JO - Neuropharmacology VL - 31 IS - 3 N2 - Synthetic benzodiazepines produce an anterograde amnesia, which can be reversed by selective benzodiazepine antagonists or inverse agonists. It has therefore been suggested that the memory-enhancing effects of the antagonists are due to antagonism of an endogenous "benzodiazepine-like" endocoid. If the memory-enhancing effects of the benzodiazepine antagonists are determined predominantly by the antagonism of such endogenous benzodiazepine-ligands, then it could be hypothesized that administration of an inverse agonist, which produces effects functionally opposite to those of benzodiazepine agonists, may also mimic the effects of benzodiazepine antagonists but not produce effects greater than those of the pure antagonists. The purpose of the present study was therefore to investigate the memory-enhancing effects of the benzodiazepine inverse agonist, ethyl-8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate (Ro 15-4513) in young HSD:(ICR)BR mice and to compare these effects with those of the benzodiazepine antagonist, flumazenil. Pretraining injections of flumazenil and Ro 15-4513 (2.5 and 10.0 mg/kg) enhanced equally, both the acquisition and the retention of a task for 1 week requiring mice to discriminate the correct arm of a T-maze, to avoid a mild electric shock. Pretreatment with Ro 15-4513 also dose-dependently protected the animals from experimental amnesia, induced by the cholinergic receptor antagonist, scopolamine in a second model of memory, in which mice were required to passively avoid a dark chamber after shock. In contrast, Ro 15-4513, injected prior to daily active avoidance sessions, failed to significantly improve either the acquisition or retention performance.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/1630596/Learning_and_memory_enhancing_effects_of_Ro_15_4513:_a_comparison_with_flumazenil_ L2 - https://medlineplus.gov/memory.html DB - PRIME DP - Unbound Medicine ER -