Influence of benzodiazepine binding site ligands on fear-conditioned contextual memory

• Published in: European journal of pharmacology Vol. 426; no. 1; pp. 45 - 54
• Main Authors: DeLorey, Timothy M, Lin, Richard C, McBrady, Brian, He, Xiaohui, Cook, James M, Lameh, Jelveh, Loew, Gilda H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 24.08.2001; Elsevier
• Subjects: Animals; Azides - pharmacology; Benzodiazepine; Benzodiazepines - metabolism; Benzodiazepines - pharmacology; Binding Sites; Binding, Competitive - drug effects; Biological and medical sciences; Carbolines - pharmacology; Conditioning (Psychology) - physiology; contextual; Convulsants - pharmacology; Fear - physiology; Fear conditioning; Flumazenil - pharmacology; GABA A receptor; GABA Antagonists - pharmacology; GABA Modulators - pharmacology; Gabaergic and benzodiazepinic system; Imidazoles - pharmacology; Ligands; Male; Medical sciences; Memory; Memory - drug effects; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; N-Methylscopolamine - metabolism; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Piperazines - pharmacology; Quinolines - pharmacology; Receptors, GABA-A - metabolism; Scopolamine - pharmacology; Silanes - pharmacology; Tritium; GABA A receptor; Memory; Benzodiazepine; Fear conditioning; Nervous system diseases; Agonist; Alzheimer disease; Ligand; Rodentia; Central nervous system; Cognition; Neuroprotective agent; Benzodiazepine receptor; Biological activity; Cerebral disorder; Vertebrata; Mammalia; Acquisition process; Mouse; Animal; Central nervous system disease; Degenerative disease; Mechanism of action; Gabaergic receptor A; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01199-2

Eight compounds that bind to the benzodiazepine binding site on the γ-amino butyric acid A (GABA A) receptor were assessed for their influence on contextual memory, an aspect of memory affected in various cognitive disorders including Alzheimer's disease. Using a Pavlovian fear-conditioning paradigm, each ligand was evaluated in C57Bl/6 mice in regards to its direct affect on contextual memory and whether the ligand could attenuate scopolamine-induced contextual memory impairment. Of the eight ligands tested, one impaired contextual memory (agonist), six attenuated scopolamine-induced contextual memory impairment (inverse agonists), and one antagonized the ability of an inverse agonist to attenuate scopolamine-induced contextual memory impairment. Hence, further demonstrating the bi-directional influence benzodiazepine binding site ligands are able to exert on memory modulation. This study serves as an initial starting point in the development of pharmacological tools to be used in deciphering how GABA A receptors influence contextual memory.