Electroconvulsive shock and neurotransmitter receptors: implications for mechanism of action and adverse effects of electroconvulsive therapy.
Neurochemical effects of electroconvulsive shock (ECS) in three neurotransmitter-receptor systems were studied in relation to the mechanism of action and adverse effects of ECT. In the noradrenergic system, chronically administered ECS, along with other effective antidepressant treatments, has been consistently reported to down-regulate beta-adrenergic receptors in rat cerebral cortex. Even when ECS was administered according to an intermittent clinically equivalent schedule, a 21% reduction in cortical 3H-DHA binding to beta-adrenoreceptors could be demonstrated 4 days after the last treatment. However, the role of presynaptic NA events in beta-adrenoreceptor down-regulation by ECS and the antidepressant mechanism of ECT remains to be clarified. Compared to the MAO inhibitor clorgyline, repeated ECS pretreatment induced only a moderate increase in NA release from a rat cortical vesicular preparation and minimally reduced the sensitivity of the preparation to release-inhibition by clonidine. In the dopaminergic system, a clinically equivalent ECS schedule had no direct effect on behavioral or biochemical indices of DA receptor sensitivity. However, the same ECS schedule significantly attenuated haloperidol-induced behaviorally and biochemically measured DA supersensitivity in the same model in which parallel effects had been reported for lithium. The possibility that a "receptor-stabilizing" mechanism may be common to ECT and lithium is considered on the basis of similarities in the clinical profiles of the two treatments. In the cholinergic system, repeated ECS significantly reduced 3H-QNB binding to muscarinic cholinergic receptors in rat cerebral cortex and hippocampus. Concurrently administered ECS also blocked the increase in 3H-QNB binding caused by chronic atropine administration. ECS effects on muscarinic cholinergic receptors may have relevance to the antidepressant mechanism of ECT.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D004565:Electroconvulsive Therapy / Q000009:adverse effects*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D018377:Neurotransmitter Agents; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D013134:Spiperone; D004082:Dihydroalprenolol; D011813:Quinuclidinyl Benzilate; D006220:Haloperidol; D009638:Norepinephrine