Intra-raphe muscimol induced hyperactivity depends on ascending serotonin projections

Abstract

Acute microinjections of the GABA agonist, muscimol (100 ng), into either the dorsal (DR) or the median (MR) raphe nucleus of etherized rats induced post-anesthesia hyperactivity as measured in photocell chambers. The increased activity counts seen after MR injections, furthermore, were 4 times greater than those following DR injections. In animals implanted with chronically indwelling cannulae, a muscimol (25-400 ng) dose-response analysis confirmed the greater sensitivity of the MR site. Subsequent experiments thus employed only MR cannulae. The benzodiazepine, chlordiazepoxide, in a subataxic dose (3.8 mg/kg, IP) by itself did not affect activity level, but enhanced the locomotor response to low doses (25-50 ng) of muscimol. Conversely, a sub-convulsant dose of the GABA antagonist, bicuculline (1.1 mg/kg, IP), completely blocked the hyperactivity produced by muscimol (50-100 ng). Bilateral electrolytic destruction of the ventral tegmental nuclei of Gudden produced hyperactivity, but failed to alter the effect of muscimol. Forebrain 5-hydroxytryptamine (5-HT, serotonin) depletion following administration of 5,7-dihydroxytryptamine did not affect baseline activity level, but markedly attenuated the locomotor response produced by intra-MR injections of muscimol. These data suggest that midbrain GABA neurons modulate activity level through a direct action on 5-HT neurons, and indicate that intra-MR muscimol induced hyperactivity depends on intact ascending 5-HT fibers.