Contribution of an alpha 1-adrenergic receptor subtype to the expression of the "ventral tegmental area syndrome"

Neuroscience. 1992;47(1):69-76. doi: 10.1016/0306-4522(92)90121-h.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Denervation
  • Dioxanes / metabolism
  • Dioxanes / pharmacology
  • Dopamine / physiology
  • Male
  • Motor Activity / drug effects
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / physiology
  • Prazosin / metabolism
  • Prazosin / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology*
  • Synaptic Transmission / drug effects
  • Tegmentum Mesencephali / anatomy & histology
  • Tegmentum Mesencephali / physiology*


  • Adrenergic alpha-Antagonists
  • Dioxanes
  • Receptors, Adrenergic, alpha
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
  • Dopamine
  • Norepinephrine
  • Prazosin