THE ROLE OF 5-HT1A AND 5-HT1B RECEPTORS IN ANTIDEPRESSANT DRUG ACTIONS IN THE MOUSE FORCED SWIMMING TEST

The forced swimming test is a behavioural model developed to predict t he efficacy of antidepressant drugs. Few studies have been aimed at ev aluating the mechanism of action of antidepressants in the forced swim ming test. The present study was designed in order to further evaluate the mode of action of antidepressants in the forced swimming test, by using selective agonists and antagonists at 5-HT1A and 5-HT1B recepto r sites. Agonists/antagonists and antidepressants were administered 45 min and 30 min, respectively, prior to testing. Prior administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1 mg/kg, i.p.) induced anti-immobility effects with the tricyclic antidepressant imip ramine (8 mg/kg, i.p.) and noradrenaline uptake inhibitors maprotiline (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.), but not with fluoxe tine (16 mg/kg, i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 m g/kg, i.p.). These effects were antagonised by prior administration of ethoxyphenyl)-4-[-(2-phthalimido)butyl]piperazine) (NAN 190) (0.5 mg/ kg, i.p.). On the other hand, pretreatment with (+/-)-pindolol (32 mg/ kg, i.p.) potentiated the effects of the selective serotonin reuptake inhibitors and was devoid of any activity with imipramine (8 mg/kg, i. p.), maprotiline (8 mg/kg, i.p.) or desipramine (16 mg/kg, i.p.). Prio r administration of methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) enhanced the antidepressant-like effects of the selective serotonin reuptake inhibitors and imipramine (8 mg/kg, i.p.) in the fo rced swimming test. The anti-immobility effects of the selective serot onin reuptake inhibitors in the forced swimming test seem to be mediat ed by presynaptic 5-HT1A receptors as well as postsynaptic 5-HT1B rece ptors. Antidepressant-like effects of the noradrenaline uptake inhibit ors seem, on the other hand, td be mediated by postsynaptic 5-HT1A rec eptors. Considering the variety of 5-HT receptors, it is possible that other subtypes may participate in the anti-immobility effects of anti depressants in the forced swimming test.