The effect of acute and repeated administration of buspirone, 8-OHDPAT and fluoxetine on haloperidol-induced extrapyramidal symptoms

OBJECTIVE: The aim of this study was to investigate the effect of buspirone, as a partial agonist of 5-HT₁A receptors, 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT) as an agonist of 5-HT₁A receptors and fluoxetine as a selective serotonin reuptake inhibitor on haloperidol-induced extrapyramidal symptoms (EPS) in male Wistar rats. MATERIALS AND METHODS: The experiments were performed on 66 male Wistar rats weighing 200-240g. The rats were divided into 11 groups (n=6). Extrapyramidal symptoms were induced by haloperidol injection 1mg/kg intraperitoneally (i.p.). To investigate the effect of serotonergic drugs on haloperidol-induced extrapyramidal symptoms, 8-OHDPAT (1 mg/kg), buspirone (10 mg/kg), and fluoxetine (1 mg/kg) were injected before haloperidol in an acute and 7 consecutive day's pre-treatment injection(s) mode. Extrapyramidal symptoms such as catalepsy and motor balance were assessed by the bar test and rotarod, respectively. FINDINGS: The results demonstrated that i.p. injection of haloperidol induced significant motor imbalance and catalepsy (p≤0.001) in rats. Data analysis showed that i.p. injection of buspirone (10 mg/kg) significantly decreased catalepsy compared with the control group. The attenuation of haloperidol-induced extrapyramidal symptoms was observed with 8-OHDPAT treatment. Treatment with fluoxetine did not affect the motor coordination caused by haloperidol. CONCLUSION: It may be concluded that buspirone and 8-OHDPAT improves extrapyramidal symptoms in a haloperidol-induced Parkinsonism model probably via activation of 5-HT₁A receptors. However, further investigations should be carried out to clarify the exact mechanism of interaction between 5-HT₁A and DA receptors.