Antidepressant-like properties of some serotonin receptor ligands and calcium channel antagonists measured with the forced swimming test in mice.

This study has examined the effects of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), buspirone, nifedipine and verapamil on duration of immobility in the forced swimming test in mice. The 5-HT1A agonist-8-OH-DPAT (0.25, 0.5, 1 mg/kg) and dihydropyridine calcium channel antagonist-nifedipine (10 mg/kg) produced decreases in immobility time. These effects were similar to those of the tricyclic antidepressant-imipramine (5 and 10 mg/kg). Non-dihydropyridine calcium channel antagonist-verapamil (10 and 20 mg/kg) had no effect on immobility time. The non-benzodiazepine anxiolytic and 5-HT1A agonist-buspirone (1 mg/kg) when given in a single injection or as repeated treatment, did not exert antidepressant-like activity in the forced swimming test. Pretreatment with dopamine antagonist-haloperidol (0.5 mg/kg) significantly antagonized the effects of 8-OH-DPAT (1 mg/kg), imipramine (10 mg/kg) and nifedipine (10 mg/kg). Pretreatment with benzodiazepine anxiolytic-diazepam (2 mg/kg) antagonized the effect of imipramine (10 mg/kg) but not that of 8-OH-DPAT (1 mg/kg) or nifedipine (10 mg/kg). Neither haloperidol nor diazepam produced any effects in this test. Single or repeated administration of buspirone (1 mg/kg) did not alter the reduction of immobility time produced by imipramine (10 mg/kg). These results suggest that 5-HT1A agonists and dihydropyridine calcium channel blockers may have antidepressant efficacy in the forced swimming test, but the effects of buspirone and 8-OH-DPAT may be mediated via different mechanisms. These results also indicate that the relationship between serotonin and dopamine neurons may play a role in the action of antidepressant drugs. In addition, the interactions involving both GABAergic and serotoninergic processes exist between benzodiazepine anxiolytics and some antidepressants.