Effects of dopamine agonists on delayed response performance in chronic low-dose MPTP-treated monkeys.
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.
Schneider
J S
JS
Center for Neurological Research, Hahnemann University, Philadelphia, PA 19102.
Sun
Z Q
ZQ
Roeltgen
D P
DP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D008251:Macaca; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D019257:Quinpirole; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D015259:Dopamine Agents; D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine