Contribution of an alpha 1-adrenergic receptor subtype to the expression of the "ventral tegmental area syndrome".
Bilateral electrolytic lesions of the rat ventral tegmental area, a mesencephalic structure containing the cell bodies of ascending dopaminergic neurons, induce a behavioural syndrome characterized by a permanent locomotor hyperactivity. Acute intraperitoneal injections of prazosin, an alpha 1-adrenergic receptor antagonist, at a dose (0.5 mg/kg) which does not affect locomotor activities of control animals, abolished locomotor hyperactivities of lesioned rats. Antagonists of other monoaminergic receptors (propranolol, ritanserin, yohimbine), and also another antagonist of alpha 1-adrenergic receptors, 2-(2',6'-dimenthoxyphenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101) were ineffective. Comparisons of autoradiograms of brain slices incubated in the presence of 1 nM [3H]prazosin or 10 nM [3H]WB4101 indicated clear topographical differences. [3H]Prazosin labelling is present in the septum and in layer III of the cerebral cortex but absent in the striatum. [3H]WB 4101 labelling is diffuse in the superficial layers of the cerebral cortex and present in the striatum. In addition, intraperitoneal injection of WB4101 displaces, only weakly, [3H]prazosin binding in layer III of the cerebral cortex (-18%) while it decreases by 50% [3H]prazosin binding in the more superficial cortical layers. These observations strongly suggest that the binding site labelled by [3H]prazosin is different from alpha 1A- and alpha 1B-adrenergic receptor subtypes labelled by [3H]WB4101. Finally, it is proposed that the prazosin-induced blockade of the locomotor hyperactivity exhibited by ventral tegmental area lesioned animals is linked to the previously demonstrated regulatory role of noradrenergic neurons on cortical dopamine transmission.
Chaire de Neuropharmacologie, INSERM U.114, Collège de France, Paris.
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F
Trovero
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Blanc
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Hervé
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Vézina
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Glowinski
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JP
Tassin
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000502:physiology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin