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Vol. 283, Issue 1, 183-189, 1997
Kunming Institute of Zoology, The Chinese Academy of Sciences,
Kunming, Yunnan, China 650223 (X.C.) and
Section of Neurobiology, Yale
Medical School, New Haven, Connecticut (A.F.T.A.)
With advancing age, monkeys develop deficits in spatial working memory
resembling those induced by lesions of the prefrontal cortex (PFC).
Aged monkeys also exhibit marked loss of dopamine from the PFC, a
transmitter known to be important for proper PFC cognitive function.
Previous results suggest that D1 agonist treatment can improve spatial
working memory abilities in aged monkeys. However, this research was
limited by the use of drugs with either partial agonist actions or
significant D2 receptor actions. In our study, the selective dopamine
D1 receptor full agonists A77636 and SKF81297 were examined in aged
monkeys for effects on the working memory functions of the PFC. Both
compounds produced a significant, dose-related effect on delayed
response performance without evidence of side effects: low doses
improved performance although higher doses impaired or had no effect on
performance. Both the improvement and impairment in performance were
reversed by pretreatment with the D1 receptor antagonist, SCH23390.
These findings are consistent with previous results demonstrating that there is a narrow range of D1 receptor stimulation for optimal PFC
cognitive function, and suggest that very low doses of D1 receptor
agonists may have cognitive-enhancing actions in the elderly.
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