Evidence that imipramine activates 5-HT sub(1C) receptor function

The anti-immobility effect of imipramine in the forced swimming test in mice was antagonized by the non-selective 5-hydroxytryptamine (5-HT) antagonist, metitepine, by the 5-HT sub(1C)/5-HT sub(2) antagonist, mesulergine and by the dopamine D sub(2) antagonist, d,l-sulpiride. These three antagonists did not alter the behaviour of imipramine-treated mice in an open-field and did not reduce imipramine brain levels. The 5-HT sub(2) antagonist, ritanserin, the 5-HT sub(1A)/5-HT sub(B) antagonist, 1-propranolol, and the 5-HT sub(3) antagonists, endo-2,3-dihydro-N-(8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2-oxo-1H -benzimidazole-1-carboxamide hydrochloride (DAU 6215) and 1,2,3,9-tetrahydro-9-methyl-3(2-methyl-1H-imidazol-1-yl)methyl)-4H -carbazol-4-one, HCl multiplied by 2H sub(2)O) (GR 38032F), failed to reduce imipramine-induced anti-immobility. Subthreshold doses of 8-hydroxy-2-(di-n-propylamino)tetralin hydrochloride (8-OH-DPAT) and imipramine did not synergize in reducing immobility. d,l-Sulpiride, but not mesulergine, antagonized the effect of desipramine in the forced swimming test.