Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys.
BACKGROUND
Dopaminergic neurotransmission is critically involved in many aspects of complex behavior and cognition beyond reward/reinforcement and motor function. Mental and behavioral disorders associated with major disruptions of dopamine neurotransmission, including schizophrenia, attention deficit/hyperactivity disorder, Parkinson's disease, Huntington's disease, and substance abuse produce constellations of neuropsychological deficits in learning, memory, and attention in addition to other defining symptoms.


OBJECTIVE
To delineate the role dopaminergic D1- and D2-like receptor subtypes play in complex brain functions.


METHODS
Monkeys (N = 6) were trained on cognitive tests adapted from a human neuropsychological assessment battery (CAmbridge Neuropsychological Test Automated Battery). The battery included tests of spatial working memory (self-ordered spatial search task), visuo-spatial associative memory and learning (visuo-spatial paired associates learning task, vsPAL) and motivation (progressive ratio task, PR). Tests of motor function (bimanual motor skill task, BMS; rotating turntable task, RTT) were also included. The effects of the dopamine D2-like antagonist raclopride (10-56 microg/kg, i.m.) and the D1-like antagonist SCH23390 (SCH, 3.2-56 microg/kg, i.m.) on cognitive performance were then determined.


RESULTS
Deficits on PR, RTT, and BMS performance were observed after both raclopride and SCH23390. Spatial working memory accuracy was reduced to a greater extent by raclopride than by SCH, which was unexpected, given prior reports on the involvement of D1 signaling for spatial working memory in monkeys. Deficits were observed on vsPAL performance after raclopride, but not after SCH23390.


CONCLUSIONS
The intriguing results suggest a greater contribution of D2- over D1-like receptors to both spatial working memory and object-location associative memory.
Von Huben
Stefani N
SN
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
Davis
Sophia A
SA
Lay
Christopher C
CC
Katner
Simon N
SN
Crean
Rebecca D
RD
Taffe
Michael A
MA
D000818:Animals; D001288:Attention / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008253:Macaca mulatta; D008297:Male; D008568:Memory / Q000187:drug effects*; D009042:Motivation; D009048:Motor Skills / Q000187:drug effects; D020891:Raclopride / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D020891:Raclopride