Back to Search
Start Over
Effects of olanzapine and betahistine co-treatment on serotonin transporter, 5-HT2A and dopamine D2 receptor binding density.
- Source :
-
Progress in Neuro-Psychopharmacology & Biological Psychiatry . Dec2013, Vol. 47, p62-68. 7p. - Publication Year :
- 2013
-
Abstract
- Abstract: Olanzapine is widely used in treating multiple domains of schizophrenia symptoms but induces serious metabolic side-effects. Recent evidence has showed that co-treatment of betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for preventing olanzapine-induced weight gain/obesity, however it is not clear whether this co-treatment affects on the primary therapeutic receptor binding sites of olanzapine such as serotonergic 5-HT2A receptors (5-HT2AR) and dopaminergic D2 receptors (D2R). Therefore, this study investigated the effects of this co-treatment on 5-HT2AR, 5-HT transporter (5-HTT) and D2R bindings in various brain regions involved in antipsychotic efficacy. Female Sprague Dawley rats were administered orally (t.i.d.) with either olanzapine (1mg/kg), betahistine (2.7mg/kg), olanzapine plus betahistine (O+B), or vehicle (control) for 2weeks. Quantitative autoradiography was used to detect the density of [3H]ketanserin, [3H]paroxetine and [3H]raclopride binding site to 5-HT2AR, 5-HTT and D2R. Compared to the controls, olanzapine significantly decreased [3H]ketanserin bindings to 5-HT2AR in the prefrontal cortex, cingulate cortex, and nucleus accumbens. Similar changes in 5-HT2AR bindings in these nuclei were also observed in the O+B co-treatment group. Olanzapine also significantly decreased [3H]paroxetine binding to 5-HTT in the ventral tegmental area and substantia nigra, however, both olanzapine only and O+B co-treatment did not affect [3H]raclopride binding to D2R. The results confirmed the important role of 5-HT2AR in the efficacy of olanzapine, which is not influenced by the O+B co-treatment. Therefore, betahistine co-treatment would be an effective combination therapy to reduce olanzapine-induced weight gain side-effects without affecting olanzapine's actions on 5-HT2AR transmissions. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 02785846
- Volume :
- 47
- Database :
- Academic Search Index
- Journal :
- Progress in Neuro-Psychopharmacology & Biological Psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 91867822
- Full Text :
- https://doi.org/10.1016/j.pnpbp.2013.08.005