Alpha up-beta down adrenergic regulation: a possible mechanism of action of antidepressant treatments.

Abstract

The presently reported findings: that spaced electroconvulsive treatment increases the density of alpha-1 adrenoceptor in the spinal cord as well as in the cerebral cortex of the rat, that treatment with various classes of antidepressant drugs, including antidepressant neuroleptics, affects in a similar manner alpha-adrenoceptors, elevating within 2 weeks the density of alpha-1, and depressing the density of alpha-2 subpopulation, and that prolonged imipramine treatment in investigated strains of rats does not depress the beta adrenoceptor density within 3 weeks, but only after 6-week-treatment such an effect is observed, are discussed together with our earlier results. It is suggested that the first effect of an antidepressant therapy may be a transient upregulation of alpha-2 adrenoceptors causing a decrease in noradrenaline utilization, but this is followed rapidly by an upregulation of alpha-1 adrenoceptors and depression of density of alpha-2 adrenoceptors. Eventually, adaptive beta adrenoceptor down-regulation follows. The final effect of an antidepressant therapy is a specific facilitation of neurotransmission regulated by alpha-1 adrenoceptors.