Effect of combined administration of 5-HT 1A or 5-HT 1B/1D receptor antagonists and antidepressants in the forced swimming test

Abstract

In the present study, we examined effects of the selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor citalopram, the 5-HT/noradrenaline reuptake inhibitor imipramine, the selective noradrenaline reuptake inhibitor desipramine or the monoamine oxidase-A inhibitor moclobemide, administered in combination with the 5-HT 1A receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}- N-(2-pyridynyl)cyclohexanecarboxamide (WAY 100635) or the 5-HT 1B/1D receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-[1,2,4]oxadiazol-3-yl)1,1′-biphenyl-4-carboxamide (GR 127935) and the 5-HT 1B receptor antagonist N-[3-(2-dimethylamino) ethoxy-4-methoxyphenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1′-biphenyl)-4-carboxamide (SB 216641) in the forced swimming test in rats. When given alone, citalopram (20 and 30 mg/kg), imipramine (20 mg/kg), desipramine (20 mg/kg), moclobemide (20 mg/kg), WAY 100635 (0.1 and 1 mg/kg), GR 127935 (10 and 20 mg/kg) or SB 216641 (2 mg/kg) did not shorten the immobility time of rats. Co-administration of WAY 100635 (0.1 and 1 mg/kg) and citalopram (20 mg/kg), or imipramine (20 mg/kg), or moclobemide (20 mg/kg) did not affect the immobility time of rats, whereas WAY 100635 given jointly with desipramine (20 mg/kg) induced a weak anti-immobility effect. GR 127935 (10 and 20 mg/kg) or SB 216641 (2 mg/kg) co-administered with imipramine, desipramine or moclobemide, but not citalopram, produced a significant anti-immobility action in the forced swimming test in rats. These results indicate that the blockade of 5-HT 1B rather than 5-HT 1A receptors may facilitate the anti-immobility effect of imipramine, desipramine or moclobemide in the forced swimming test. No interaction was observed between 5-HT 1A or 5-HT 1B/1D receptor antagonists and citalopram.