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.
Toide
K
K
Department of Pharmacology, Taiho Pharmaceutical Co., Ltd, Tokushima, Japan.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D000547:Amantadine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid