ANXIOLYTIC NATURAL AND SYNTHETIC FLAVONOID LIGANDS OF THE CENTRAL BENZODIAZEPINE RECEPTOR HAVE NO EFFECT ON MEMORY TASKS IN RATS

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 h igh affinity to the central benzodiazepine receptor, and to exert powe rful anxiolytic and other benzodiazepine-like effects in rats. Their c hemical analog, quercetin, shares none of these effects. In the presen t article we find that, in contrast to diazepam, chrysin, apigenin, an d 6,3'-dinitroflavone have no amnestic effect on acquisition or retent ion of three different learning tasks (inhibitory avoidance, shuttle a voidance, 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 giv en posttraining, on test session retention, of crossing responses in t he open field and hindered retention of inhibitory avoidance, and show ed no anxiolytic action in an elevated plus maze. Unlike diazepam, non e of these drugs had any analgesic effect in the tail-flick test. The data suggest that chrysin, apigenin, and 6,3'-dinitroflavoine, three f lavonoids derivatives possessing anxioselective effects acting on cent ral benzodiazepine receptors, may deserve clinical trials as anxiolyti c agents. (C) 1997 Elsevier Science Inc.