Enhanced 5-hydroxytryptamine and dopamine-mediated behavioural responses following convulsions—III the effects of monoamine antagonists and synthesis inhibitors on the ability of electroconvulsive shock to enhance responses |
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Authors: | AR Green DW Costain JFW Deakin |
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Institution: | 1. MRC Unit and University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford OX2 6HE England;2. National Institute for Medical Research, Mill Hill, London NW7, England |
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Abstract: | Repeated electroconvulsive shock (ECS) administration to rats resulted in enhanced 5-hydroxytryptamine 5-HT) and dopamine (DA) mediated behavioural responses. Pretreatment with p-chlorophenylalanine before the course of ECS (over 10 days) abolished the enhancement of 5-HT mediated responses but not the enhancement of DA-mediated responses. Pretreatment of rats just before each ECS with either of the 5-HT antagonists (?)-propranolol (20 mg/kg) or methergoline (5 mg/kg) also abolished the enhancement of 5-HT but not DA-mediated responses. In contrast, pretreatment with haloperidol (0.5 mg/kg) before each ECS did not inhibit the enhancement of 5-HT or DA-mediated responses. α-Methyl p-tyrosine administration during the course of ECS administration abolished both the enhancement of 5-HT and DA-mediated responses. Specific depletion of the brain noradrenaline content by neurotoxin lesioning did not alter the behavioural responses to either the 5-HT agonist quipazine or the dopamine agonist apomorphine. However, following ECS, lesioned animals did not show the enhanced response to these agonists that was seen in the sham operated rats.The data therefore suggest that intact 5-HT synthesis and release is important for ECS to enhance 5-HT mediated responses, but not to enhance DA-mediated responses. Electroconvulsive shock-induced enhancement of DA-mediated responses does not require intact brain DA synthesis, consistent with other published data, and intact brain NA systems (α-methyl p-tyrosine and lesioning results) are required for ECS to produce enhanced responses of both 5-HT and DA-mediated behavioural resnonses. |
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Keywords: | electroconvulsive shock 5-hydroxytryptamine-mediated behaviour dopamine-mediated behavior electroconvulsive shock monoamine synthesis |
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