RAPID DECREASE IN RAT-BRAIN BETA-ADRENERGIC-RECEPTOR BINDING DURING COMBINED ANTI-DEPRESSANT ALPHA-2 ANTAGONIST TREATMENT

  • 1 January 1983
    • journal article
    • research article
    • Vol. 224  (3) , 640-646
Abstract
The delay in onset of the therapeutic effect of antidepressants is believed to be due to a progressive decrease in the density of central .beta.-adrenergic receptors. The changes in .beta.-adrenergic receptor density could result from an increase in the synaptic concentration of norepinephrine, which is secondary to a decrease in the sensitivity of the .alpha.2-adrenergic receptor which normally inhibits release and the firing of the locus ceruleus. An acceleration of .beta.-receptor desensitization with combined administration of antidepressants and .alpha.2-adrenergic antagonists was observed. After 1 day of administration of desipramine (DMI) with phenoxybenzamine, there was a marked decrease in .beta.-adrenergic receptor density. One day of treatment with DMI alone had no significant effect on .beta.-receptor density. Rapid desensitization occurs not only in rat limbic cortex, but also in hippocampus and mesencephalon. Combination therapy of DMI with yohimbine or dihydroergotamine, both .alpha.2-adrenergic blockers, is similar to DMI-phenoxybenzamine treatment. Combined administration with prazosin, an .alpha.2-antagonist, had no effect on antidepressant-induced desensitization. Combined administration of .alpha.2-antagonists accelerated .beta.-receptor desensitization by amitryptyline, mianserin, iprindole, tranylcypromine and pargyline. Pharmacological blockade of .alpha.2-adrenergic receptors apparently enhances antidepressant-induced decreases in CNS .beta.-adrenergic receptor density.

This publication has 0 references indexed in Scilit: