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January 1986

Biochemical and Functional Evidence of Supersensitive Platelet α2-Adrenoceptors in Major Affective Disorder: Effect of Long-term Lithium Carbonate Treatment

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.

Arch Gen Psychiatry. 1986;43(1):51-57. doi:10.1001/archpsyc.1986.01800010053007

• The hypothesis that depressive illness is related to supersensitive α2-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 α2-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 α2-adrenoceptor that recognizes agonists and mediates physiological effects.

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