Журнал высшей нервной деятельности им. И.П. Павлова, 2020, T. 70, № 4, стр. 473-487

THE EFFECT OF CHRONIC ADMINISTRATION OF BUSPIRONE, 8-OHDPAT AND DIFFERENT DOSES OF FLUOXETINE ON HALOPERIDOL INDUCED EXTRAPYRAMIDAL DISORDERS AND GENERAL LOCOMOTOR ACTIVITY IN MALE RATS

Mohammadmahdi Sabahi 1, Sara Ami Ahmadi 1, Rasool Haddadi 2***

1 Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences
Hamadan, Iran

2 Department of Pharmacology and Toxicology, Medicinal plant and natural products Research Center, School of Pharmacy, Hamadan University of Medical Sciences
Hamadan, Iran

* E-mail: haddadi.rasool@gmail.com
** E-mail: haddadi.r@umsha.ac.ir

Поступила в редакцию 28.03.2019
После доработки 1.12.2019
Принята к публикации 16.12.2019

Аннотация

Objective.

Buspirone is a partial agonist of 5HT1A receptors, 8-OHDPAT (8-Hydroxy-2-(dipropylamino) tetralin) is an agonist of 5HT1A receptors, and fluoxetine is a serotonin uptake inhibitor. Among 5-HT receptor subtypes, 5-HT1A receptor plays a crucial role in modulating extrapyramidal motor disorders, including antipsychotic-induced extrapyramidal symptoms. Aim. This study aimed to investigate the effect of chronic administration of buspirone, 8-OHDPAT and different doses of fluoxetine on haloperidol-induced extrapyramidal disorders and general locomotor activity in male rats. Methods. Extrapyramidal disorders were induced by haloperidol injection 1mg/kg intraperitoneally (i.p.). To investigate the effect of serotonergic drugs on haloperidol-induced extrapyramidal disorders, we used 8-OHDPAT (1 mg/Kg), buspirone (10 mg/Kg), and fluoxetine (0.5 mg/Kg and 1 mg/Kg) as a chronic injection. Following this, the different groups of rats were placed in a rotarod, bar test and open field test apparatus, where their behavior and locomotor activity during these tasks were recorded respectively. Findings. Data analysis showed that i.p. injection of fluoxetine (0.5 mg/Kg and 1 mg/Kg), buspirone (10 mg/kg) and 8-OHDPAT (1 mg/Kg) decreased catalepsy compared with the control group (p < 0.001). The attenuation of haloperidol-induced motor imbalance was observed with fluoxetine (0.5 mg/Kg) just in 15th day of treatment (p < 0.001), fluoxetine (1 mg/Kg) in all days (p < 0.001), 8-OHDPAT (1mg/Kg) in all days (p < 0.05) and buspirone (10 mg/kg) just in 10th and 15th day of treatment (p < 0.001). Conclusion. It may be concluded that fluoxetine, buspirone, and 8-OHDPAT improve extrapyramidal disorders and locomotor impairment in haloperidol-induced Parkinsonism model through activation of nigral 5HT1A receptors.

Keywords: Buspirone, Fluoxetine, general locomotor activity, Haloperidol, 8-OHDPAT

DOI: 10.31857/S0044467720040097

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