Effects of dexfenfluramine on dopamine dependent behaviours in rats

5-hydroxytryptamine (5-HT) inhibits the synthesis and release of dopamine (DA) from rat nigrostriatal DAergic neurons. Dexfenfluramine releases 5-HT from brain 5-HTergic neurons. The present study was undertaken to determine whether dexfenfluramine, through the released 5-HT, modulates the intensity of the behaviours dependent on the functional status of the nigrostriatal DAergic system. The effect of pretreatment with dexfenfluramine on dexamphetamine and apomorphine stereotypies of the oral movement variety and on catalepsy induced by haloperidol and small doses (0.05 and 0.1 mg/kg ip) of apomorphine was studied in rats. We also investigated whether dexfenfluramine induces catalepsy in rats. Dexfenfluramine at 2.5, 5 and 10 mg/kg ip did not induce catalepsy and did not antagonise apomorphine stereotypy. However, 1 h pretreatment with 5-HT releasing doses of dexfenfluramine ie 5 and 10 mg/kg ip, antagonized dexamphetamine stereotypy and potentiated catalepsy induced by haloperidol and small doses of apomorphine. Our results, that dexfenfluramine at 2.5, 5 and 10 mg/kg ip neither induced catalepsy nor antagonised apomorphine stereotypy, indicate that dexfenfluramine at these doses does not block the postsynaptic striatal D2 and D1 DA receptors. They also indicate that the 5-HT released by 5 and 10 mg/kg dexfenfluramine does not exert an inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptor sites. However, 5 and 10 mg/kg doses of dexfenfluramine, through the released 5-HT, inhibit the synthesis and release of DA from the nigrostriatal DAergic neurons and thus antagonise dexamphetamine stereotypy and potentiate catalepsy induced by haloperidol and small doses of apomorphine.