Amantadine increases l-DOPA-derived extracellular dopamine in the striatum of 6-hydroxydopamine-lesioned rats

• Published in: Brain research Vol. 972; no. 1; pp. 229 - 234
• Main Authors: Arai, Akira, Kannari, Kazuya, Shen, Huo, Maeda, Tetsuya, Suda, Toshihiro, Matsunaga, Muneo
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 16-05-2003; Amsterdam Elsevier; New York, NY
• Subjects: Adrenergic Agents - toxicity; Amantadine; Amantadine - pharmacology; Analysis of Variance; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Aromatic l-amino acid decarboxylase; Aromatic-L-Amino-Acid Decarboxylases - metabolism; Benserazide - pharmacology; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - injuries; Corpus Striatum - metabolism; Dialysis - methods; Dopamine; Dopamine - metabolism; Dopamine Agents - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors - pharmacology; Extracellular Space - metabolism; l-DOPA; Levodopa - metabolism; Male; Medical sciences; Neuropharmacology; Oxidopamine - toxicity; Parkinson’s disease; Pharmacology. Drug treatments; Rats; Rats, Wistar; Striatum; Time Factors; Striatum; Amantadine; Dopamine; l-DOPA; Aromatic l-amino acid decarboxylase; Neurotransmitters, modulators, transporters, and receptors; Parkinson’s disease; Animal model; Parkinson's disease; Rat; Rodentia; Central nervous system; Parkinson disease; Basal ganglion; Corpus striatum; Extracellular; Vertebrata; Mammalia; Aromatic L-amino acid decarboxylase; L-DOPA; Levodopa; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)02531-9

We investigated the effect of amantadine on
l-DOPA-derived extracellular dopamine (DA) levels and aromatic
l-amino acid decarboxylase (AADC) activity in the striatum of rats with nigrostriatal dopaminergic denervation by 6-hydroxydopamine (6-OHDA). Pretreatment with 30 mg/kg amantadine increased the cumulative amount of extracellular DA in the striatum of 6-OHDA-lesioned rats treated with 10 mg/kg benserazide and 50 mg/kg
l-DOPA to 250% of that without amantadine (
P<0.01). Under pretreatment with 10 mg/kg benserazide, AADC activity after 30 mg/kg amantadine administration was reduced to 43% of controls (
P<0.01). Amantadine-induced increase in
l-DOPA-derived extracellular DA provides the basis for the clinical usefulness of amantadine in combination with
l-DOPA. However, the effect of amantadine on
l-DOPA-derived extracellular DA may not be caused by changes in AADC activity.