The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys

被引:50
作者
Arnsten, AFT
Murphy, B
Merchant, K
机构
[1] Yale Univ, Sch Med, Neurobiol Sect, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA
[3] Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA
关键词
memory; prefrontal cortex; stress; dopamine; D4; receptors; FG7142K;
D O I
10.1016/S0893-133X(00)00133-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 oft he 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. (C) 2000 American College of Neuropsychopharmacology.
引用
收藏
页码:405 / 410
页数:6
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