Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model

Area of Science:

• Pharmacology
• Neuroscience
• Metabolic Research

Background:

• Olanzapine effectively treats schizophrenia but causes significant metabolic side effects, including weight gain and obesity.
• Antipsychotic-induced weight gain is linked to histamine H₁ receptor antagonism.
• Histamine H₁ receptors play a crucial role in regulating body weight and appetite.

Purpose of the Study:

• To investigate the potential of betahistine, a histamine H₁ receptor agonist and H₃ receptor antagonist, to mitigate olanzapine-induced weight gain.
• To evaluate the effects of combined betahistine and olanzapine treatment on body weight, food intake, and feeding efficiency in a rat model.

Main Methods:

• Female Sprague Dawley rats received oral administration of olanzapine and/or betahistine, or vehicle, for two weeks.
• Body weight, food intake, feeding efficiency, and locomotor activity were monitored.
• Statistical analysis was performed to compare treatment groups.

Main Results:

• Olanzapine treatment led to significant body weight gain and increased food intake.
• Co-treatment with betahistine significantly prevented weight gain by 45% and reduced feeding efficiency compared to olanzapine alone.
• Betahistine monotherapy did not affect weight gain or food intake; olanzapine reduced locomotor activity, but betahistine did not alter this effect.

Conclusions:

• Combined treatment with betahistine can partially counteract olanzapine-induced body weight gain and reduce feeding efficiency.
• Betahistine's H₃ receptor antagonistic effects may increase histamine release, potentially enhancing its H₁ agonistic effects to manage weight gain.
• These findings suggest betahistine's potential utility in clinical settings for managing antipsychotic-induced obesity.