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Stress exposure impairs the cognitive functioning of the prefrontal cortex (PFC). Previous research has examined the dopamine (DA) D1 receptor mechanisms underlying this response. The current study performed a preliminary examination of the role of D4 receptor mechanisms by determining whether the selective D4 receptor antagonist, PNU-101387G, could prevent stress-induced working memory deficits in monkeys. Animals were tested on the delayed response task following treatment with PNU-101387G (0 or 0.1-0.8 mg/kg, 60-min pretreatment), and the pharmacological stressor, FG7142 (0 or 0.2 mg/kg, 30-min pretreatment). FG7142 significantly impaired delayed response performance relative to vehicle; PNU-101387G pretreatment produced a dose-related reversal of the FG7142 response. PNU-101387G had no significant effects on its own, but there were trends toward improvement at low doses and impairment at higher doses. Further studies in a larger number of animals appear warranted. These preliminary findings suggest that D4 receptor mechanisms contribute to stress-induced cognitive dysfunction.

The Selective Dopamine D4 Receptor Antagonist, PNU-101387G, Prevents Stress-Induced Cognitive Deficits in Monkeys