The effects of dopamine and its antagonists on directional delay-period activity of prefrontal neurons in monkeys during an oculomotor delayed-response task.
To examine the role of dopamine receptors in the memory field of neurons for visuospatial working memory in the prefrontal cortex (PFC), dopamine and its antagonists (SCH23390 for the D1-antagonist and sulpiride for the D2-antagonist) were applied iontophoretically to neurons of the dorsolateral PFC in monkeys that performed an oculomotor delayed-response task. In this task, the subject made a memory-guided saccade to a remembered target location that had been cued by a visuospatial stimulus (right, up, left, or down; 15 degrees in eccentricity) prior to a 4-s delay period. We focused here on PFC neurons that showed directional delay-period activity; i.e., an increased activity during the delay period, the magnitude of which varied significantly with the target location. Iontophoretic application of SCH23390 (usually 50 nA) decreased or increased the activities of most of these neurons (n=48/62, 77%); most neurons showed a decrease (n=43/62, 69%). For the neurons affected by SCH23390, a directional index of directional delay-period activity was attenuated by SCH23390, whereas the preferred direction was not greatly affected. The decreasing effect of SCH23390 was dose-dependent; the extent of the decrease was less with a lower dose (20-nA current) than with the ordinary dose (50-nA current), although the effect of the lower dose of SCH23390 on delay-period activity was similar in nature to that of the ordinary dose of SCH23390. Furthermore, the application of dopamine itself augmented directional delay-period activity in most of the neurons tested (n=12/16, 75%). Sulpiride did not have any significant effects in most of the neurons tested (n=15/17). These results suggest that the activation of D1-dopamine receptors play a facilitating role in the memory field of PFC neurons for visuospatial working memory processes.
Sawaguchi
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Laboratory of Neurobiology, Graduate School of Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan. toshi-sw@med.hokudai.ac.jp
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D016208:Databases, Factual; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005133:Eye Movements / Q000187:drug effects / Q000502:physiology; D007478:Iontophoresis; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D012438:Saccades / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D004298:Dopamine