Locomotor response to L-DOPA in reserpine-treated rats following central inhibition of aromatic L-amino acid decarboxylase: further evidence for non-dopaminergic actions of L-DOPA and its metabolites

Neurosci Res. 2010 Sep;68(1):44-50. doi: 10.1016/j.neures.2010.06.003. Epub 2010 Jun 11.


L-DOPA is the most widely used treatment for Parkinson's disease. The anti-parkinsonian and pro-dyskinetic actions of L-DOPA are widely attributed to its conversion, by the enzyme aromatic L-amino acid decarboxylase (AADC), to dopamine. We investigated the hypothesis that exogenous L-DOPA can induce behavioural effects without being converted to dopamine in the reserpine-treated rat-model of Parkinson's disease. A parkinsonian state was induced with reserpine (3 mg/kg s.c.). Eighteen hours later, the rats were administered L-DOPA plus the peripherally acting AADC inhibitor benserazide (25 mg/kg), with or without the centrally acting AADC inhibitor NSD1015 (100 mg/kg). L-DOPA/benserazide alone reversed reserpine-induced akinesia (4158+/-1125 activity counts/6 h, cf vehicle 1327+/-227). Addition of NSD1015 elicited hyperactive behaviour that was approximately 7-fold higher than L-DOPA/benserazide (35755+/-5226, P<0.001). The hyperactivity induced by L-DOPA and NSD1015 was reduced by the alpha(2C) antagonist rauwolscine (1 mg/kg) and the 5-HT(2C) agonist MK212 (5 mg/kg), but not by the D2 dopamine receptor antagonist remoxipride (3 mg/kg) or the D1 dopamine receptor antagonist SCH23390 (1 mg/kg). These data suggest that L-DOPA, or metabolites produced via routes not involving AADC, might be responsible for the generation of at least some L-DOPA actions in reserpine-treated rats.

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism*
  • Benserazide / pharmacology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Disease Models, Animal
  • Dopamine Agents / metabolism
  • Dopamine Agents / pharmacology
  • Drug Combinations
  • Dyskinesia, Drug-Induced / enzymology*
  • Dyskinesia, Drug-Induced / physiopathology
  • Enzyme Inhibitors / pharmacology
  • Hydrazines / pharmacology
  • Hyperkinesis / chemically induced
  • Hyperkinesis / enzymology
  • Hyperkinesis / physiopathology
  • Levodopa / metabolism*
  • Levodopa / pharmacology*
  • Male
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reserpine / pharmacology*
  • Serotonin Receptor Agonists / pharmacology


  • Adrenergic Uptake Inhibitors
  • Adrenergic alpha-Antagonists
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Dopamine Agents
  • Drug Combinations
  • Enzyme Inhibitors
  • Hydrazines
  • Serotonin Receptor Agonists
  • benserazide, levodopa drug combination
  • Levodopa
  • Benserazide
  • Reserpine
  • 3-hydroxybenzylhydrazine
  • Aromatic-L-Amino-Acid Decarboxylases