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.
Biała
G
G
Department of Pharmacodynamics, Medical Academy, Lublin, Poland.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001569:Benzodiazepines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003866:Depressive Disorder / Q000523:psychology*; D007099:Imipramine / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D018490:Serotonin Agents / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013550:Swimming / Q000523:psychology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D002121:Calcium Channel Blockers; D008024:Ligands; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; D007099:Imipramine