The overall objectives of this research are to compare the effects of administration of electroconvulsive shock (ECS) and antidepressant drugs on serotonergic and noradrenergic receptors in rat brain. In particular, the following hypotheses will be tested: 1) that ECS differs from most antidepressant drug treatments in its effects on 5-HT-2 receptors, and 2) that ECS differs from most antidepressant drug treatments in its effects on up-regulated beta-adrenergic receptors. To test the latter hypothesis, we will use a new model in which following highly specific lesions of 5-HT neurons or inhibition of 5-HT synthesis, beta-adrenergic receptors are markedly increased in brain. Among the specific aims of this research are: 1) To determine the effects of ECS and antidepressant drugs on the increased number of beta-adrenergic receptors by measuring ligand binding and isoproterenol-stimulated cyclic AMP production in brain. 2) To use quantitative autoradiography to identify and compare the specific brain regions in which beta-adrenergic receptors are decreased by ECS and antidepressant drugs, and to identify the beta receptor subtype affected by these treatments. 3) To identify by quantitative autoradiography the specific regions and layers of cerebral cortex in which 5-HT-2 receptors are increased by ECS and decreased by antidepressant drugs. 4) To compare the effects of ECS and antidepressant drugs on 5-HT-2 and alpha-1-adrenergic receptor-mediated phosphoinositide hydrolysis. 5) To determine whether lesions of norepinephrine axons alter the effects of ECS or antidepressant drugs on 5-HT-2 receptors. These studies should provide new information about the effects of ECS and antidepressant drugs on the receptor systems for the two neurotransmitters that have been most often implicated in depression and its treatment. This information should contribute to an eventual understanding of the neurochemical effects of ECS and antidepressant drugs and potentially to the rationale for the clinical effects of electroconvulsive therapy.
