Elsevier

Brain Research

Volume 92, Issue 2, 11 July 1975, Pages 291-306
Brain Research

Research report
Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine

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Abstract

By means of single unit recording techniques it was found that a small systemically administered (intravenous) dose of the α-adrenergic agonist clonidine inhibited the spontaneous firing of brain norepinephrine (NE)-containing neurons in the locus coeruleus. In addition, the NE neurons were consistently inhibited by the direct (microiontophoretic) application of minute amounts of NE or clonidine. Intravenous clonidine also inhibited the firing of the great majority of 5-hydroxytryptamine (5-HT) neurons in the midbrain dorsal raphe nucleus. However, this action does not appear to be a direct one since clonidine (and NE) had relatively weak or variable effects when applied microiontophoretically to raphe neurons. The clonidine-induced depression of raphe firing may be secondary to an impairment in adrenergic transmission since (1) the depression could be reversed by the NE-releasing agents d- and l-amphetamine, (2) high doses of clonidine itself (which have been reported to have postsynaptic α-agonistic activity) reversed the depression produced by a low dose of clonidine and (3) prior destruction of NE neurons by 6-hydroxydopamine (7–12 days) rendered raphe neurons insensitive to the depressant effect of i.v. clonidine. Dopaminergic (substantia nigra, zona compacta) neurons did not respond to either low or high doses of clonidine. These results are consistent with previous data showing that clonidine decreases NE and 5-HT but not dopamine turnover. We conclude that systemically administered clonidine inhibits the firing of brain NE neurons by acting directly upon adrenergic receptors located on or near the soma of these neurons but that the concomitant inhibition of 5-HT neurons is an indirect effect (possibly secondary to an impairment in noradrenergic transmission).

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  • Cited by (0)

    Present address: Department of Pharmacology, University of Göteborg, Fack S-400 33, Göteborg 33, Sweden.

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