Abstrait

Effect of Antidepressant Fluoxetine A SSRI on Dopamine Dependent Behaviours in Rats

Kanhaiah More, Vandana M Thorat, Anjali R Shinde, and Jehangir J Balsara

5-hydroxytryptamine (5-HT) inhibits the synthesis and release of dopamine (DA) from rat nigrostriatal neurons. Fluoxetine, a bicyclic antidepressant, enhances serotonergic neurotransmission through potent and selective inhibition of neuronal reuptake of 5-HT. The present study was undertaken to determine whether fluoxetine, through its 5-HT neuronal reuptake inhibiting action, modulates the intensity of the behaviours dependent on the functional status of the nigrostriatal DAergic system. The effect of pretreatment with fluoxetine on dexamphetamine and apomorphine stereotypies of the oral movement variety and on catalepsy induced by haloperidol and small dose of apomorphine was studied in rats. We have also investigated whether fluoxetine induces catalepsy in rats. Our results, that fluoxetine at 2.5, 5, 10 and 20 mg/kg ip neither induced catalepsy nor antagonised apomrphine stereotypy, indicate that fluoxetine at these doses does not block the postsynaptic striatal D2 and D1 DA receptors. It also indicates fluoxetine at 5, 10, 20 mg/kg increase 5-HT neurotransmission by SSRI mechanism and doesnot exert an inhibitory effect at or beyond the postsynaptic striatal D2 and D1, DA receptor sites. Fluoxetine at 5, 10, 20 mg/kg doses increase 5-HT neurotransmission through serotonin SSRI mechanism, inhibit synthesis and release of DA from the nigrostriatal DAergic neurons and thus potentiate catalepsy induced by haloperidol and small dose apomorphine. But, however 10 and 20 mg/kg ip fluoxentine potentiate dexamphetamine stereotypy.