Modulation of second messenger function in rat brain by in vivo alteration of receptor sensitivity: relevance to the mechanism of action of electroconvulsive therapy and antidepressants.
1. The second messengers cyclic AMP and inositol triphosphate are the intracellular mediators for a number of neurotransmitters for which receptors exist on brain neurons. 2. Up- or down-regulation of these receptors in general produce corresponding changes in the associated second messenger systems. 3. Chronic administration of antidepressants including electroconvulsive shock to rats produces a number of changes in cerebral receptors, notably down-regulation of beta-adrenergic and serotonin 5-HT2 receptors and up-regulation of alpha-1 adrenergic receptors. 4. The changes in receptor number induced by such antidepressant treatments are in general accompanied by corresponding changes in the associated second messenger reactions. 5. Antidepressant administration has also been shown to induce increased post-receptor mediated adenylate cyclase activity in cortical membranes, and similar effects have also been reported in striatum after chronic administration of neuroleptics. The relevance of these effects to the mechanism of action of the drugs is discussed.
Newman
M E
ME
Jerusalem Mental Health Center-Ezrath Nashim, Israel.
Lerer
B
B
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy; D004597:Electroshock; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems
D000928:Antidepressive Agents; D011956:Receptors, Cell Surface