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.
Trovero
F
F
Chaire de Neuropharmacologie, INSERM U.114, Collège de France, Paris.
Blanc
G
G
Hervé
D
D
Vézina
P
P
Glowinski
J
J
Tassin
J P
JP
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