Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT_1A and 5-HT_1B receptors in old mice

Abstract.

Rationale: A recent study suggested that selective serotonin reuptake inhibitors were inactive in 40-week-old male mice in the mouse forced swimming test, possibly because of alteration of 5-HT₁ receptors. Objectives: The present study was aimed at investigating the action of various antidepressant drugs in 4- and 40-week-old male mice using the mouse forced swimming test and determining the involvement of 5-HT_1A and 5-HT_1B receptors mediating the effects. Methods: Different classes of antidepressants [imipramine (tricyclic), maprotiline (noradrenline reuptake inhibitor), venlafaxine (mixed serotonin and noradrenaline reuptake inhibitors), fluvoxamine and sertraline (selective serotonin reuptake inhibitor)] were tested in the same randomised experimental session, alone and in combination with 5-HT_1A and 5-HT_1B receptor agonists [buspirone (partial 5-HT_1A agonist), anpirtoline (5-HT_1B agonist)] in the mouse forced swimming test. Results: All antidepressants were found to be active in the mouse forced swimming test in 4-week-old mice and 40-week-old mice, with the exception of fluvoxamine in the 40-week-old mice. The anti-immobility effect after antidepressant administration was higher in 4-week-old male mice than in 40-week-old male mice. Venlafaxine is the most active antidepressant drug in 40-week-old mice. Prior administration of buspirone (0.06 mg/kg, IP) or anpirtoline (1 mg/kg, IP) enhanced the antidepressant-like effects in 4-week-old mice (except in the case of sertraline, 8 mg/kg). In elderly mice, only prior administration of buspirone enhanced the antidepressant-like effects of fluvoxamine. A neurochemical study showed that significantly higher serotonin and dopamine concentrations were found in 40-week-old control mice brains than 4-week-old control mice brains but that the noradrenaline concentration is higher in 4-week-old mice. Conclusion: Tricyclic, noradrenaline reuptake inhibitors and serotonin reuptake inhibitors are more active in 4-week-old mice than 40-week-old mice. Our results suggested that 5-HT_1B receptors may be more altered than 5-HT_1A receptors in 40-week-old mice.