, 207:119 | Cite as

Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors

  • Shona L. Kirk
  • John Glazebrook
  • Ben Grayson
  • Joanna C. Neill
  • Gavin P. Reynolds
Original Investigation



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.


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.


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.


Antipsychotic drug Olanzapine Weight gain Rat 5-HT2C receptor Histamine H1 receptor 


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Shona L. Kirk
    • 1
  • John Glazebrook
    • 2
  • Ben Grayson
    • 2
  • Joanna C. Neill
    • 2
  • Gavin P. Reynolds
    • 1
  1. 1.Department of PsychiatryQueen’s University BelfastBelfastUK
  2. 2.Bradford School of PharmacyUniversity of BradfordBradfordUK

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