The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task.
1. To examine the role of dopamine receptors in the prefrontal cortex (PFC) on working memory, we injected dopamine antagonists (SCH23390, SCH39166, haloperidol, sulpiride, and raclopride) locally into the dorsolateral PFC in two monkeys trained to perform an oculomotor delayed-response (ODR) task. In the ODR task, monkeys fixate a central spot on a cathode ray tube (CRT) monitor while a visual cue is briefly (300 ms) presented in one of several peripheral locations in the visual field. After a delay of 1.5-6 s, the fixation spot is turned off, instructing the monkey to move its eyes to the target location that had been indicated by the visuospatial cue before the delay. Each monkey also performed a control task in which the cue remained on during the delay period. In this task the monkey's response was sensory rather than memory guided. 2. Local intracerebral injection of the selective dopamine antagonists SCH23390 (10-80 micrograms) and SCH39166 (1-5 micrograms) and/or the nonselective dopamine antagonist haloperidol (10-100 micrograms) induced deficits in ODR task performance at a total of 22 sites in the dorsolateral PFC. The deficit was characterized by a decrease in the accuracy of the memory-guided saccade as well as an increase in the latency of the response. The deficit usually appeared within 1-3 min after the injection, reached a peak at 20-40 min, and recovered at 60-90 min. 3. Performance change was restricted to a few specific target locations, which varied with the injection site and were most often contralateral to the injection site. 4. The degree of impairment in the ODR task occasioned by the injection of the dopamine antagonists was sensitive to the duration of delay; longer delays were associated with larger decreases in the accuracy and delayed onset of the memory-guided saccade. 5. The deficit was dose dependent; higher doses induced larger errors and increases in the onset of the memory-guided saccade. 6. Dopamine antagonists did not affect performance on the control task, which required the same eye movements but was sensory guided. Thus, in the same experimental session in which ODR performance was impaired, the accuracy and the latency of the sensory-guided saccades were normal for every target location.(ABSTRACT TRUNCATED AT 400 WORDS)
Sawaguchi
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Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Goldman-Rakic
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PS
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists; D005133:Eye Movements / Q000187:drug effects / Q000502:physiology*; D005403:Fixation, Ocular / Q000187:drug effects / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D007267:Injections; D007650:Ketanserin / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D009949:Orientation / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D020891:Raclopride; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D012438:Saccades / Q000187:drug effects / Q000502:physiology; D012457:Salicylamides / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D012457:Salicylamides; C058081:ecopipam; D020891:Raclopride; D013469:Sulpiride; D007650:Ketanserin; D006220:Haloperidol; D004298:Dopamine