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Biochemical and Functional Evidence of Supersensitive Platelet 2-Adrenoceptors in Major Affective Disorder

Effect of Long-term Lithium Carbonate Treatment

Jesús A. García-Sevilla, MD; José Guimón, MD; Pascual García-Vallejo, MD; María Josefa Fuster, MD

Arch Gen Psychiatry. 1986;43(1):51-57.

Abstract
• The hypothesis that depressive illness is related to supersensitive 2-adrenoceptors in the brain has been tested indirectly in blood platelets. The binding of tritiated clonidine hydrochloride to platelet membranes, a ligand that labels only the high-affinity state of the 2-adrenoceptor that is coupled with cell functions, and the aggregation response induced by epinephrine hydrochloride, which is the result of the activation of the high-affinity state, were measured and correlated in 13 patients with major affective disorder. Both the number of high-affinity binding sites and the aggregation response were increased in depressed patients. There was a negative and significant correlation between both measures in the same depressed patients. Treatment with lithium carbonate (Plenur [Spain]; Linthane, comparable US product) was associated with a decrease in the high-affinity state and with an increase in the aggregation response. Thus, major affective disorder may be related to a dysfunction of the high-affinity state of the 2-adrenoceptor that recognizes agonists and mediates physiological effects.

Author Affiliations
From the Departments of Pharmacology (Drs García-Sevilla, GarcíaVallejo, and Fuster) and Psychiatry (Dr Guimón), University of the Basque Country Medical School, Leioa, Vizcaya, Spain.

Footnotes
Accepted for publication March 11, 1985.

Read in part at the International Union of Pharmacology Ninth International Congress of Pharmacology, London, Aug 1, 1984, and at the Fall Meeting of the American Society for Pharmacology and Experimental Therapeutics, Indianapolis, Aug 22, 1984.

Reprint requests to Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad del País Vasco, Leioa, Vizcaya, Spain (Dr García-Sevilla).

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