Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors
SL Kirk, J Glazebrook, B Grayson, JC Neill… - …, 2009 - Springer
SL Kirk, J Glazebrook, B Grayson, JC Neill, GP Reynolds
Psychopharmacology, 2009•SpringerIntroduction Substantial increases in body weight can be induced by several antipsychotic
drugs, most notably olanzapine and clozapine. Antagonism at certain receptors, particularly
5-HT2C and histamine H1 receptors, is implicated in this effect. Materials and methods We
have investigated the contribution of effects at these receptors to olanzapine-induced weight
gain occurring over 5 days following daily intraperitoneal drug injections in groups of eight
female rats. Results Olanzapine (2 mg/kg) and the 5-HT2C antagonist SB 243213 (1 mg/kg) …
drugs, most notably olanzapine and clozapine. Antagonism at certain receptors, particularly
5-HT2C and histamine H1 receptors, is implicated in this effect. Materials and methods We
have investigated the contribution of effects at these receptors to olanzapine-induced weight
gain occurring over 5 days following daily intraperitoneal drug injections in groups of eight
female rats. Results Olanzapine (2 mg/kg) and the 5-HT2C antagonist SB 243213 (1 mg/kg) …
Introduction
Substantial increases in body weight can be induced by several antipsychotic drugs, most notably olanzapine and clozapine. Antagonism at certain receptors, particularly 5-HT2C and histamine H1 receptors, is implicated in this effect.
Materials and methods
We have investigated the contribution of effects at these receptors to olanzapine-induced weight gain occurring over 5 days following daily intraperitoneal drug injections in groups of eight female rats.
Results
Olanzapine (2 mg/kg) and the 5-HT2C antagonist SB 243213 (1 mg/kg), but not the histamine H1 antagonist mepyramine (1 mg/kg), produced significant increases in percentage body weight above vehicle; olanzapine showed a significantly greater effect than SB 243213. Haloperidol (0.1 mg/kg) alone or with mepyramine had no significant effects on weight gain, while with SB 243213 and with both SB 243213 and mepyramine, it showed olanzapine-like increases in weight.
Conclusion
These results suggest that 5-HT2C receptor antagonism or inverse agonism, in the presence of D2 receptor antagonism, may contribute to olanzapine-induced weight gain.
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