Effect of Mirtazapine Pre-treatment on Haloperidol, Ergometrine and Fluoxetine Induced Behaviours in Albino Rats.

ABSTRACT

Background: Central 5-HT and 5-HT serotonergic 2A 2Creceptors are mainly involved in the control ofnigrostriatal and mesolimbic dopaminergic neuronalactivity has been well proved and established. 5-HThas facilitatory effect on stimulated dopamine releaseby stimulating central 5-HT receptors and inhibitory 2Aeffect by stimulating 5-HT receptors. Aim and 2CObjectives: To evaluate 5-HT and 5-HT receptor 2A 2Cblocking activity of Mirtazapine (MIR) and the effectof mirtazapine pre-treatment on Ergometrine (ERG)induced behaviours, Fluoxetine (FLU) induced penileerections and Haloperidol (HAL) induced catalepsy inrats. Material and Methods: Each group wassubdivided into different subgroups consisting 6animals in each. Control group received DimethylSulfoxide (DMSO) and other groups received differentdoses of mirtazapine one hour before ERG/FLU/HAL.Values obtained from control group were comparedwith all remaining groups pre-treatment with differentdoses of MIR. Results: MIR (MIR) at 2.5, 5, 10 and 20mg/kg intraperitoneally (i.p) did not produce any per seeffects. Pre-treatment with 5, 10 and 20 mg/kg i.p. MIRsignificantly antagonised ERG induced behaviours. 5mg/kg i.p. MIR significantly antagonised whereas 10and 20 mg/kg i.p. MIR abolished FLU (10 mg/kg)induced penile erections in rats. MIR 5 and 20 mg/kgi.p. significantly antagonised HAL (1mg/kg) inducedcatalepsy at 1 hr testing time interval while 10 and 20mg/kg MIR significantly antagonised HAL (1 mg/kg)induced catalepsy at 2 hr testing time interval.Conclusion: Our results indicate that MIR at 5, 10 and20 mg/kg possesses 5-HT and 5-HT receptors 2A 2Cblocking activity. At 5, 10 and 20 mg/kg MIR, byblocking central 5-HT receptors predominantly, 2Ccauses release of dopamine from nigrostriataldopaminergic neurons and therefore antagonizes HALinduced catalepsy