Effects of housing and muricidal behavior on serotonergic receptors and interactions with novel anxiolytic drugs

Abstract

Mouse killing by rats represents a predatory behavior that can be modified by drugs from several different therapeutic classes and by environmental conditions. Buspirone and gepirone, non-benzodiazepine anxiolytics that stimulate serotonergic receptors (5HT_1a) and inhibit isolation-induced intraspecies aggression, were tested for inhibition of muricidal behavior by isolated rats. Neither buspirone (3.0 mg/kg s.c.) nor gepirone (from 5.0 to 40 mg/kg) inhibited muricide. Additional rats were housed, either aggregated or isolated, and tested for muricidal behavior 9 times over 5 weeks to establish which animals were muricidal: thus, there were 4 groups of rats: muricidal or non-muricidal under either isolated or aggregated housing condition. [³H]-Spiperone was used to determine striatal D₂ receptor Bmax and K_d and prefrontal cortex D₂ and 5HT₂ receptor binding. There were no changes across the four groups. Binding of [³H]-5-hydroxytryptamine (5HT) to 5HT_1a receptors decreased in septum of both groups of isolated rats and binding to 5HT_1b receptors decreased 50% in hippocampus of isolated and aggregated muricidal rats. Binding of [³H]-5HT to either receptor was unchanged in amygdaloid area and hypothalamus across all groups. Thus, stimulating pre- and postsynaptic 5HT_1a receptors does not alter muricidal behavior and changes in 5HT₁ receptor binding occurs in limited areas. Whether this limited change in hippocampal 5HT_1b binding is important for establishing muricidal behavior is unclear; however the direction of the change is consistent with reports that decreased serotonergic activity increases predatory behavior.