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

Abstract

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.

• Authors: Shona L Kirk, John Glazebrook, Ben Grayson, Joanna C Neill, Gavin P Reynolds
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 207 Issue 1 Pg. 119-25 (Nov 2009) ISSN: 1432-2072 [Electronic] Germany
• PMID: 19688201 (Publication Type: Journal Article)

Chemical References

• Dopamine Antagonists
• Histamine H1 Antagonists
• Indoles
• Pyridines
• Receptor, Serotonin, 5-HT2C
• Receptors, Histamine H1
• Serotonin 5-HT2 Receptor Agonists
• Serotonin Uptake Inhibitors
• Benzodiazepines
• Pyrilamine
• Haloperidol
• Olanzapine
• SB 243213

Topics

• Analysis of Variance
• Animals
• Behavior, Animal (drug effects)
• Benzodiazepines (pharmacology)
• Dopamine Antagonists (pharmacology)
• Drug Interactions
• Female
• Haloperidol (pharmacology)
• Histamine H1 Antagonists (pharmacology)
• Indoles (pharmacology)
• Olanzapine
• Pyridines (pharmacology)
• Pyrilamine (pharmacology)
• Rats
• Receptor, Serotonin, 5-HT2C (physiology)
• Receptors, Histamine H1 (physiology)
• Serotonin 5-HT2 Receptor Agonists
• Selective Serotonin Reuptake Inhibitors (pharmacology)
• Time Factors
• Weight Gain (drug effects)