Long term effects of olanzapine and betahistine on serotonin 5-HT2A receptor binding in the rat brain
Olanzapine is widely used in treating multiple domains of schizophrenia symptoms through its binding profiles to various neurotransmitter receptors including 5-HT2A receptors (5-HT2AR). Our previous studies have shown that 2 weeks co-treatment of betahistine (a H1R agonist and H3R antagonist) could reduce obesity induced by olanzapine. This study aimed to investigate whether long term co-treatment of olanzapine and betahistine affects 5-HT2AR bindings. Methods: Female Sprague- Dawley rats were administered under 4 conditions (n=12): (1) Rats were treated with vehicle (control) during whole experimental period; (2) Cotreatment group (O+B): 5 weeks olanzapine treatment (1 mg/kg, t.i.d.), followed by 6 weeks co-administration of olanzapine with betahistine (9.6 mg/kg, t.i.d.); (3) olanzapine only (1 mg/kg, t.i.d.) treatment during weeks 7-11; (4) betahistine only (9.6 mg/kg, t.i.d.) treatment during weeks 7-11. Density of 5-HT2AR were measured using [³H]ketanserin. Results: Compared to the controls, olanzapine significantly decreased 5-HT2AR bindings in accumbens shell and substantia nigra (SN) (p
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