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


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.


CONCLUSIONS
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.
Kirk
Shona L
SL
Department of Psychiatry, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Glazebrook
John
J
Grayson
Ben
B
Neill
Joanna C
JC
Reynolds
Gavin P
GP
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D000077152:Olanzapine; D011725:Pyridines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
D001569:Benzodiazepines; D018492:Dopamine Antagonists; D006220:Haloperidol; D006634:Histamine H1 Antagonists; D007211:Indoles; D000077152:Olanzapine; D011725:Pyridines; D011738:Pyrilamine; D044405:Receptor, Serotonin, 5-HT2C; D011969:Receptors, Histamine H1; D058826:Serotonin 5-HT2 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C406343:SB 243213
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