[H-3]-ketanserin binding and elevated plus-maze behavior after chronic antidepressant treatment in DSP-4 and P-CPA pretreated rats: Evidence for partial involvement of 5-HT2A receptors

[H-3]-Keranserin binding in mt neocortex (frontal and cerebral cortex) afte r 3-week treatment with desipramine (10 mg/kg) and citalopram (5 mg/kg) in vehicle-, DSP-4- (50 mg/kg) and p-CPA- (350 mg/kg before the beginning of e xperiments and once per week on the first and second week plus 100 mg/kg in the last week) pretreated rats was measure. The antidepressant activity of DSP-4 and p-CPA was evaluated indirectly using the elevated plus-maze rest . Acute antidepressant treatment revealed an anxiogenic effect while chroni c treatment elicited an anxiolytic effect. DSP-I and p-CPA pretreatment eli cited an antiexploratory effect that was not blocked by acute antidepressan t treatment. After 3 weeks of antidepressant treatment, only desipramine DSP-4 or p-CPA treatment revealed an antiexploratory effect Three-week anti depressant treatment downregulated [H-3]-keranserin binding in the cerebral cortex. Citalopram treatment partially reversed p-CPA-induced down-regulat ion of [H-3]-ketanserin binding in mt whole neocortex. In conclusion, our e xperiments suggest that the 5 -HT2A receptors in monoamine-impaired mrs are involved in the mediation of antidepressant-induced behavioural phenomena, but chronic antidepressant treatment downregulates [H-3]-ketanserin in bin ding independently from the state of monoaminergic neurotransmission. (C) 1 999 Prous Science. All rights reserved.