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Comparative effects of olanzapine and ziprasidone on hypophagia induced by enhanced histamine neurotransmission in the rat
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posted on 2023-06-07, 18:24 authored by Nimaa Davoodi, Mikhail Kalinichev, Pete CliftonPete CliftonAtypical antipsychotic drugs (AAPDs), such as olanzapine, are associated with weight gain and hyperphagia in both humans and rodents. This side effect, however, is absent or reduced for AAPD such as ziprasidone. The increased levels of appetite seen in rodents may be related to drug interactions with brain histamine systems involved in appetite control. We demonstrate a significant interaction of olanzapine treatment with histamine neurotransmission in a rat-feeding paradigm measuring the consumption of a palatable fat emulsion. This interaction was identified using the H3 receptor antagonist thioperamide, which by blocking autoreceptor control of histaminergic neurons enhances release of hypothalamic histamine, causing hypophagia. We challenged this effect of thioperamide with olanzapine, which among its pharmacological actions is a potent H1 receptor antagonist. Olanzapine pretreatment significantly attenuated thioperamide-induced hypophagia. Pretreatment of thioperamide with ziprasidone, an AAPD with negligible H1 receptor affinity, however, failed to have this effect. Although thioperamide may also increase levels of neurotransmitters other than histamine, the potent H1 antagonist property of olanzapine is likely to result in the suppression of thioperamide-induced hypophagia. We conclude that olanzapine may be directly modulating histaminergic neurotransmission associated with the regulation of feeding behaviour.
History
Publication status
- Published
Journal
Behavioural PharmacologyISSN
0955-8810External DOI
Issue
2Volume
19Page range
121-128Pages
8.0Department affiliated with
- Psychology Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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