3033221

Presynaptic alpha-2 adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline release (as measured by in vivo dialysis) in the rat.

Article date: 1987/5/1

PubMed ID: 3033221

Journal name: The Journal of pharmacology and experimental therapeutics (ISSN: 0022-3565)

ABSTRACT

Transcortical dialysis in awake unrestrained rats has been used to evaluate the functional role of differently located alpha-2 adrenoceptors in mediating the action of the alpha-2 adrenoceptor antagonist idazoxan on cerebral noradrenaline release. Basal efflux of noradrenaline collected by a cortically implanted dialysis fiber was stable over a period of 4 days. Systemic injections of idazoxan (20 mg/kg i.p.) increased cortical noradrenaline efflux. This effect was potentiated by pretreatment with the noradrenaline uptake blocker desipramine (20 mg/kg i.p.). Local cortical infusion of (10(-4) M idazoxan which provides a theoretical extracellular administration of 4 to 48 microM) via the dialysis fiber, thus eliminating the potential contribution of somatodendritic alpha-2 adrenoceptors, also elevated cortical noradrenaline efflux. Desipramine (20 mg/kg i.p.) potentiated this effect. Four days after lesioning cortical cell bodies with ibotenic acid (20 min infusion of 10(-4) M ibotenic acid via the dialysis fiber), both systemic injections and local cortical infusions of idazoxan were still effective in increasing cortical noradrenaline efflux. Lesion of serotonergic afferents to the cerebral cortex (by i.c.v. injection of 5,7-dihydroxytryptamine) or of cortical cholinergic afferents (by bilateral electrocoagulation of the nucleus basalis magnocellularis) did not affect the ability of cortical idazoxan infusion to stimulate noradrenaline efflux. The results suggest that the effects of idazoxan on cortical noradrenaline release are mediated primarily by alpha-2 adrenoceptors on noradrenergic nerve terminals, rather than by those located postsynaptically, somatodendritically or on the terminals of other neuronal inputs to the cerebral cortex.

Author List: Dennis T, L'Heureux R, Carter C, Scatton B

Publication Types: Journal Article

Substances mentioned in the article: Dioxanes; Dioxins; Receptors, Adrenergic, alpha; Ibotenic Acid; 5,7-Dihydroxytryptamine; Desipramine; Norepinephrine; Idazoxan;

Mesh terms: 5,7-Dihydroxytryptamine/administration & dosage; Animals; Cerebral Cortex/drug effects; Desipramine/pharmacology; Dioxanes/pharmacology; Dioxins/pharmacology; Drug Synergism; Electrocoagulation; Ibotenic Acid/pharmacology; Idazoxan; Injections, Intraventricular; Male; Norepinephrine/metabolism; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha/metabolism;

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