ABSTRACT

Parkinson's disease is characterized by a loss of dopamine neurons comprising the nigrostriatal pathway. Replacement therapy with the dopamine precursor, levodopa, initially provides symptomatic relief to most patients. This chapter reviews the effects of both acute and chronic alterations in dopaminergic neurotransmission on striatal immediate-early gene (IEG) expression and presents recent evidence suggesting that IEGs may contribute to modifications in the response to levodopa possibly by modulating neuropeptide gene expression. Chronic administration of levodopa fails to restore the normal balance between striatopallidal and striatonigral neuropeptides, but rather creates a new equilibrium that depends on the constancy with which it is delivered. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys midbrain dopamine neurons in both humans and monkeys producing a syndrome that closely resembles Parkinson's disease. Like humans afflicted with Parkinson's disease, MPTP-treated monkeys develop akinesia, bradykinesia, rigidity, stooped posture and tremor.