title: The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys.
abstract: 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.
authors.affiliation: Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Arnsten
authors.forename: B
authors.initials: B
authors.lastname: Murphy
authors.forename: K
authors.initials: K
authors.lastname: Merchant
mesh_terms: D000818:Animals; D002243:Carbolines; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D018756:GABA Antagonists; D008253:Macaca mulatta; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050638:Receptors, Dopamine D4; D013315:Stress, Psychological / Q000139:chemically induced; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D002243:Carbolines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018756:GABA Antagonists; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D013449:Sulfonamides; C035874:FG 7142; C100448:sonepiprazole; D000096926:Benzenesulfonamides