Involvement of 5-HT(2) receptor in imipramine-induced hyperglycemia in mice.

Effects of imipramine on plasma glucose levels were investigated in mice. Imipramine i. p. induced dose-dependent hyperglycemia, which was enhanced by pretreatment with 5-HT (1/2/5/7) receptor antagonist methysergide and 5-HT (2A/2B/2C) receptor antagonist LY 53857. 5-HT (2C/2B) receptor antagonist SB 206553 also augmented imipramine-induced hyperglycemia although 5-HT (1A) and 5-HT (1B) receptor antagonist (-)-propranolol,5-HT (2A) receptor antagonist ketanserin and 5-HT (3/4) receptor antagonist tropisetron each had no effect. Imipramine i. p.-induced hyperglycemia was antagonized by the 5-HT (2C/2B) receptor agonist 1-(3-chlorophenyl)piperazine (mCPP), while the 5-HT (2B) receptor agonist BW 723C86 had no effect. Intracerebroventricular injection of imipramine also elevated plasma glucose levels, which is enhanced by SB 206553. Hyperglycemia elicited by central injection of imipramine was abolished by adrenalectomy. These results suggest that imipramine-induced hyperglycemia in mice is related to its inhibition of the central 5-HT (2C) receptor. Moreover, our results indicate that adrenaline release is related to imipramine-induced hyperglycemia.