title: 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.
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008636:Mesencephalon / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000187:drug effects
chemical_list: D010080:Oxazoles; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D009118:Muscimol; D002707:Chlordiazepoxide; D001640:Bicuculline