Effects of amantadine on dopaminergic neurons in discrete regions of the rat brain

The effect of a dopamine agonist, amantadine, on dopaminergic neurons was investigated in rat brains. Amantadine (40 mg/kg, i.p.) tended to increase DA (16%) and DOPAC (24%) levels. Further, amantadine (40 mg/kg, i.p.) significantly increased HVA levels in frontal cortex (44% above baseline after 40 mg/kg, i.p.) but not in corpus striatum and nucleus accumbens. Amantadine significantly increased DA levels at doses of 10, 20 and 40 mg/kg, i.p., in corpus striatum. On the other hand, amantadine decreased the L-DOPA accumulation by 30% in frontal cortex. This decreasing effect of amantadine may be attributable to a negative feedback mechanism by DA autoregulation. Our findings, therefore, suggest that amantadine may accelerate dopaminergic neurotransmission by increasing DA release from the frontal cortex and may possibly improve senile dementia.