[3H]-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.

[3H]-Ketanserin binding in rat neocortex (frontal and cerebral cortex) after 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 experiments and once per week on the first and second week plus 100 mg/kg in the last week) pretreated rats was measured. The antidepressant activity of DSP-4 and p-CPA was evaluated indirectly using the elevated plus-maze test. Acute antidepressant treatment revealed an anxiogenic effect while chronic treatment elicited an anxiolytic effect. DSP-4 and p-CPA pretreatment elicited an antiexploratory effect that was not blocked by acute antidepressant treatment. After 3 weeks of antidepressant treatment, only desipramine + DSP-4 or p-CPA treatment revealed an antiexploratory effect. Three-week antidepressant treatment downregulated [3H]-ketanserin binding in the cerebral cortex. Citalopram treatment partially reversed p-CPA-induced downregulation of [3H]-ketanserin binding in rat whole neocortex. In conclusion, our experiments suggest that the 5-HT2A receptors in monoamine-impaired rats are involved in the mediation of antidepressant-induced behavioral phenomena, but chronic antidepressant treatment downregulates [3H]-ketanserin binding independently from the state of monoaminergic neurotransmission.