Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex

Abstract

The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg-1, twice daily for 14 days) and acute administration of the beta-adrenoceptor, clenbuterol, on 5-hydroxytryptamine (5-HT)- and dopamine-mediated behaviours in mice have been examined. All three treatments enhanced the carbidopa/5-hydroxytryptophan (5-HTP)-induced head-twitch response at all doses of 5-HTP examined, producing a parallel shift in the dose-response curve. A single ECS administration or single dose of desmethylimipramine had no effect. Only repeated ECS enhanced the locomotor response to injection of apomorphine. The dose-response curve shift was not parallel. A single ECS had no effect. A 6-hydroxydopamine lesion of brain dopamine terminals also enhanced the apomorphine response, but again did not produce a parallel shift in the dose-response curve. Both repeated ECS and repeated desmethylimipramine administration to rats increased the number of 5-HT2 receptor sites in rat brain. Clenbuterol had no effect. The enhancing effects of repeated ECS and clenbuterol administration on the 5-HTP-induced head-twitch response were additive. Enhanced 5-HT-mediated behavioural responses are seen in both mice and rats after these treatments. If it is assumed, therefore, that similar receptor changes occur in both species it appears that there is no relationship in either behavioural system between the ability of the treatment to alter receptor number and the change in the dose-response curve (parallel or non-parallel). All three antidepressant treatments (ECS, a tricyclic and a beta-adrenoceptor agonist) increase 5-HT-mediated behavioural responses although clenbuterol did not increase 5-HT2 receptor number. Only ECS increased dopamine-mediated responses.