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 [H-3]prazosin or 10 nM [H-3]WB4101 indicated clear topographical differences. [H-3]Prazosin labelling is present in the septum and in layer III of the cerebral cortex but absent in the striatum. [H-3]WB 4101 labelling is diffuse in the superficial layers of the cerebral cortex and present in the striatum. In addition, intraperitoneal injection of WB 4101 displaces, only weakly, [H-3]prazosin binding in layer III of the cerebral cortex (-18%) while it decreases by 50% [H-3]prazosin binding in the more superficial cortical layers. These observations strongly suggest that the binding site labelled by [H-3]prazosin is different from alpha(1A)- and alpha(1B)-adrenergic receptor subtypes labelled by [H-3]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.