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Effects of dopamine agonists on delayed response performance in chronic low-dose MPTP-treated monkeys
J S Schneider1, Z Q Sun, D P Roeltgen
1Center for Neurological Research, Hahnemann University, Philadelphia, PA 19102.
Abstract:
Monkeys exposed to low doses of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) develop difficulty in performing a previously learned delayed response (DR) task. In the present group of animals, performance deficits were manifested as a combination of mistakes or incorrect responses and no response errors, trials on which the animals failed to respond. Methylphenidate and the dopamine D2 receptor agonist LY-171555, at low doses, decreased the number of no-response errors but not mistakes. The partial D1 agonist SKF-38393 had no effects on no-response errors or mistakes. Thus, behavioral deficits associated with decreased task persistence may be amenable to treatment with dopamine agonists, and particularly D2 agonists, while cognitive performance per se may not be improved by such drugs. The similarities between this primate model and the cognitive/behavioral deficits associated with early Parkinson's disease and attention deficit hyperactivity disorder suggest that this may be a useful model for testing hypotheses concerning the pharmacological treatment of these disorders.
Insights
Dopamine agonists, especially D2 agonists, may help improve task persistence in models of Parkinson's disease and ADHD. However, these drugs may not enhance overall cognitive performance in such conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Primate Models
Background:
- Dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure in monkeys impairs performance on delayed response (DR) tasks.
- Deficits manifest as incorrect responses and failure to respond (no-response errors).
Purpose of the Study:
- To investigate the effects of dopamine agonists on MPTP-induced behavioral deficits in a primate model.
- To differentiate the impact of D1 and D2 receptor agonists on cognitive performance and task persistence.
Main Methods:
- Monkeys were administered low doses of MPTP to induce neurotoxicity.
- Behavioral performance on a DR task was assessed.
- The effects of methylphenidate, D2 agonist LY-171555, and D1 agonist SKF-38393 were evaluated.
Main Results:
- Methylphenidate and LY-171555 reduced no-response errors but did not improve incorrect responses.
- SKF-38393 showed no significant effect on either error type.
- Behavioral deficits related to task persistence were targeted by D2 agonists.
Conclusions:
- Dopamine D2 agonists show potential for treating behavioral deficits associated with decreased task persistence in MPTP-treated primates.
- Cognitive performance itself may not be improved by these dopaminergic treatments.
- This primate model offers insights for pharmacological treatments of Parkinson's disease and ADHD.