EFFECTS OF DOPAMINE ANTAGONISTS ON NEURONAL-ACTIVITY RELATED TO A DELAYED-RESPONSE TASK IN MONKEY PREFRONTAL CORTEX

1. Using iontophoretic techniques, we investigated the influence of dopamine (DA) antagonists [haloperidol (HAL), a non-selective DA antagonist; sulpiride (SUL), a selective antagonist for D2 receptors; and fluphenazine (FLU), a potent antagonist for D1 receptors] on neuronal activity related to a delayed response (DR) task in the monkey prefrontal cortex (PFC). The DR task was initiated by the rotation of a handle to a central zone and consisted of seven distinct periods: an initial intertrial interval of 0.3 s, a precue period of 1 s (a center green lamp), a cue period of 2 s (left or right lamp), a delay period of 4 s, a go period (red lamp in the center; rotation of the handle to either the left or right zone), a hold period (holding of the handle in eighter the left or right zone), and a final reward period. Because it was shown, as described in the companion paper (Sawaguchi et al. 1990), that DA augments the increased activity of prefrontal neurons related to the cue, delay, and go periods of the DR task, effect of the DA antagonists were examined in a total of 61 neurons that showed increases in activity related to these periods and a response to DA. 2. Consistent with previous studies (Sawaguchi et al. 1988a, 1990), iontophoretically applied DA increased DR task-related activity in prefrontal neurons. Iontophoretically applied HAL and FLU antagonized the increased effect of DA on the task-related activity. By contrast, SUL did not have any clear effects on the influence of DA. 3. By themselves, HAL and FLU reduced prefrontal neuronal activity related to the cue, delay, and go periods of the DR task. The ratio of the reduction by HAL and FLU was significantly larger for activity during the cue, delay or go period than for background activity during the precue period; as a result, the signal-to-noise (S/N) ratio of the task-related activity to background-activity was reduced during application of HAL and FLU. In contrast, SUL did not have any clear effect on activity related to the cue, delay, and go periods of the DR task, and the S/N ratio during the application of SUL did not significantly differ from that before the appliction of the drug. Furthermore, in the neurons that showed differential activity (see previous paper, Sawaguchi et al. 1990) related to the cue, delay and/or go periods, the application of HAL or FLU caused differential activity to cease to be differential, whereas the application of SUL did not have a significant effect on differential activity. 4. It is concluded that an activation of DA receptors, probably of D1-type receptors, is responsible for increased activity in prefrontal neurons related to the performance of the DR task. It is suggested that the activation of D1 receptors and, hence, of DA-sensitive enzymes, may be associated with prefrontal neuronal processes involved in the temporal organization of behaviors guided by spatial short-term memory.