title: Clonidine: attenuation of sedative action by facilitated central noradrenergic neurotransmission.
abstract: Administration of clonidine, 0.05 mg/kg i.p. to mice 30 min before trial significantly depressed the exploration of a Y-maze. This effect was completely antagonized by 1-amphetamine, 0.75 mg/kg i.p., given 10 min before trial, which by itself did not change the behaviour studied. The clonidine-induced behavioural depression also appeared reduced after pretreatment with desipramine (10 mg/kg i.p., 30 min before clonidine) which, like l-amphetamine, by itself was inactive. The above treatment with clonidine significantly reduced the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase both in the noradrenaline (NA) rich neocortex and the dopamine-rich neocortex and the dopamine-rich corpus striatum, whereas the dopa accumulation in the limbic brain regions was not significantly affected. l-Amphetamine, 0.75 mg/kg i.p., did not by itself significantly affect the dopa accumulation, but reduced the clonidine-induced effects. The results are compatible with the notion that the depression of exploratory behaviour by clonidine is related to impaired central NA-neurotransmission and rule out the possibility that it is due to activation of central post-synaptic NA-(alpha-)-receptors.
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D051379:Mice
chemical_list: D006834:Hydrazines; D004295:Dihydroxyphenylalanine; D000661:Amphetamine; D003000:Clonidine; D003891:Desipramine