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Repeated Ecs Selectively Enhances 5-Ht2 Receptor Mediated Neuroendocrine Responses in the Rat

Repeated electroconvulsive shock (ECS) has marked effects on the biochemistry and function of central 5-HT receptors. The 5-HTlA mediated behavioural syndrome in the rat is attenuated by repeated ECS (Goodwin et al. (1987) Psychopharmacology 91 : 500-505), whilst both the number of 5-HT2 receptors in the rat, and the 5-HT2 receptor mediated head twitch in the mouse, are increased by repeated ECS (Goodwin et al. (1984) Br J Pharmacol 83: 235-242). The secretion of the anterior pituitary hormone ACTH is under the stimulatory control of 5-HT. The selective ligands 8-hydroxy-2-(di-npropylamino)tetralin (8-OHDPAT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (Hoyer (1988) J Receptor Res 8 : 59-81) stimulate release of ACTH by their agonist activity at 5-HTIA and 5-HT2 receptors respectively. In the present study we used the ACTH responses to 8-OHDPAT and DOI to determine the effects of repeated ECS on a neuroendocrine model of 5-HTIA and 5-HT2 receptor mediated function in the rat. Groups of 6-9 male Sprague-Dawley rats (200-300g) received 5 ECS treatments over 10 days, applied via ear clip electrodes under halothane anaesthesia. Sham treated animals received halothane anaesthesia alone. On the morning following the last treatment, groups of animals were injected with saline (lml/kg i.p.), 8-OHDPAT (0.1 and 0.5mg/kg s.c.), or DOI (lmg/kg i.p.). Animals were sacrificed by decapitation 20 minutes later, and trunk blood collected into lithium heparin tubes. Plasma was separated by centrifugation and stored frozen until assay. ACTH was measured by a direct triple antibody immunoradiometric assay. Data are mean±SEM. Differences between means were assessed by unpaired Student’s t-test. There was no significant effect of ECS treatment on basal (saline treated) ACTH levels (73±31.3 vs 130±76.8 pg/ml; sham vs ECS). Similarly, there was no significant effect of ECS treatment on the ACTH response to the 5-HTIA receptor agonist 8-OHDPAT at either O.lmg/kg (211±82.2 vs 293±71.2 pg/ml; sham vs ECS) or 0.5 mg/kg (833±92.8 vs 912±76.7 pg/ml; sham