title: [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.
abstract: [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.
authors.affiliation: Department of Pharmacology, University of Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Skrebuhhova
authors.forename: L
authors.initials: L
authors.lastname: Allikmets
authors.forename: V
authors.initials: V
authors.lastname: Matto
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001596:Benzylamines / Q000494:pharmacology*; D001665:Binding Sites; D015283:Citalopram / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology*; D007650:Ketanserin / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014316:Tritium
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D001596:Benzylamines; D014179:Neurotransmitter Uptake Inhibitors; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015283:Citalopram; D014316:Tritium; D007650:Ketanserin; C012102:DSP 4; D010134:Fenclonine; D003891:Desipramine