Anxiolytic Natural and Synthetic Flavonoid Ligands of the Central Benzodiazepine Receptor Have No Effect on Memory Tasks in Rats

• Published in: Pharmacology, biochemistry and behavior Vol. 58; no. 4; pp. 887 - 891
• Main Authors: Salgueiro, J.B, Ardenghi, P, Dias, M, Ferreira, M.B.C, Izquierdo, I, Medina, J.H
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-1997; Elsevier Science
• Subjects: Animals; Anti-Anxiety Agents - pharmacology; Anxiolytic action; Apigenin; Avoidance Learning - drug effects; Biological and medical sciences; Chamomile; Chrysin; Diazepam; Diazepam - pharmacology; Dinitroflavone; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Effects on analgesia; Effects on memory; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Ligands; Male; Medical sciences; Memory - drug effects; Oils, Volatile - pharmacology; Pharmacology. Drug treatments; Plants, Medicinal; Psychomotor Performance - drug effects; Quercetin; Quercetin - pharmacology; Rats; Rats, Wistar; Reaction Time - drug effects; Receptors, GABA-A - drug effects; Toxicity: nervous system and muscle; Chrysin; Effects on memory; Apigenin; Quercetin; Anxiolytic action; Dinitroflavone; Effects on analgesia; Diazepam; Agonist; Rat; Pharmacognosy; Psychotropic; Toxicity; Memory; Rodentia; Instrumental conditioning; Benzodiazepine receptor; Retention; Flavonoid; Learning; Vertebrata; Mammalia; Acquisition process; Tranquillizer; Animal; Plant origin
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(97)00054-3

The naturally occurring flavonoids, chrysin (5,7-dihydroxyflavone) and apigenin (5,7,4′-trihydroxyflavone), and the synthetic compound, 6,3′-dinitroflavone have been recently reported to selectively bind with high affinity to the central benzodiazepine receptor, and to exert powerful anxiolytic and other benzodiazepine-like effects in rats. Their chemical analog, quercetin, shares none of these effects. In the present article we find that, in contrast to diazepam, chrysin, apigenin, and 6,3′-dinitroflavone have no amnestic effect on acquisition or retention of three different learning tasks (inhibitory avoidance, shuttle avoidance, and habituation to an open field), even when given at doses higher than those previously reported to be anxiolytic. Apigenin had a slight enhancing effect on training session performance and, when given posttraining, on test session retention, of crossing responses in the open field and hindered retention of inhibitory avoidance, and showed no anxiolytic action in an elevated plus maze. Unlike diazepam, none of these drugs had any analgesic effect in the tail-flick test. The data suggest that chrysin, apigenin, and 6,3′-dinitroflavoine, three flavonoids derivatives possessing anxioselective effects acting on central benzodiazepine receptors, may deserve clinical trials as anxiolytic agents.