Many neuropsychiatric and neurologic diseases including, schizophrenia, alcoholism, drug abuse, Alzheimer's, Parkinson's and HIV infection are associated with significant cognitive symptoms which substantially impact illness outcome. Rather than global cognitive deficits, studies that have used measures of selective cognitive tasks suggest that these patient groups exhibit impaired functioning in specific domains, implicating disruption in focal brain regions or systems. Animal models are valuable for investigating the role of particular neurochemical systems and neuroanatomical regions in the complex behavioral processes underlying cognition. A neuropsychological test battery employing a touch-sensitive computer screen has been developed to detect changes in cognitive performance in rhesus monkeys. The battery includes probes of memory, learning, attention, motor performance and reaction-time, as well as an estimate of relative reinforcement efficacy. The proposed studies offer a testable hypothesis for manipulating the dopamine, norepinephrine, acetylcholine and amino acid neurotransmitter systems with the goal of determining their respective contributions to cognitive function, focusing on domains that may be especially vulnerable to chronic drug abuse. Sensitive behavioral paradigms will be employed to test predictions about the likely functions of these neural systems and compare the functioning of these systems in a common behavioral context.
The specific aims are: To identify the neuropharmacological substrates mediating the cognitive processes of I) learning (concurrent visual discrimination) and memory (pattern recognition, spatial working and visuo-spatial memory), II) vigilance, attention, motivation and, III) motor skill. Individual tasks within the battery permit comparisons between the effects of manipulations of different transmitter systems, while comparisons across tests allow a more comprehensive evaluation of the function of each system. The information gained will then offer 1) further evidence for behavioral homology among cognitive testing between human and nonhuman primates 2) knowledge on the relative contribution of distinct neurochemical systems, and more precisely the specific pharmacological substrates, for performance in different neurocognitive domains. These results will help to elucidate the deficits observed in various human diseases and animal models of these diseases, aiding in the interpretation of the clinical sequelae and pointing to potential pharmacotherapies that may be useful for treating specific aspects of neurocognitive dysfunction.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-1 (01))
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Schnur, Paul
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Scripps Research Institute
La Jolla
United States
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Taffe, Michael A (2012) ??Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques. J Psychopharmacol 26:1299-306
Taffe, Michael A; Taffe, William J (2011) Rhesus monkeys employ a procedural strategy to reduce working memory load in a self-ordered spatial search task. Brain Res 1413:43-50
Taffe, Michael A; Lay, Christopher C; Von Huben, Stefani N et al. (2006) Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys. Drug Alcohol Depend 82:276-81
Von Huben, Stefani N; Davis, Sophia A; Lay, Christopher C et al. (2006) Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys. Psychopharmacology (Berl) 188:586-96
Madden, Lisa J; Flynn, Claudia T; Zandonatti, Michelle A et al. (2005) Modeling human methamphetamine exposure in nonhuman primates: chronic dosing in the rhesus macaque leads to behavioral and physiological abnormalities. Neuropsychopharmacology 30:350-9
Taffe, Michael A; Weed, Michael R; Gutierrez, Tannia et al. (2004) Modeling a task that is sensitive to dementia of the Alzheimer's type: individual differences in acquisition of a visuo-spatial paired-associate learning task in rhesus monkeys. Behav Brain Res 149:123-33
Katner, Simon N; Davis, Sophia A; Kirsten, Amber J et al. (2004) Effects of nicotine and mecamylamine on cognition in rhesus monkeys. Psychopharmacology (Berl) 175:225-40
Katner, Simon N; Flynn, Claudia T; Von Huben, Stefani N et al. (2004) Controlled and behaviorally relevant levels of oral ethanol intake in rhesus macaques using a flavorant-fade procedure. Alcohol Clin Exp Res 28:873-83
Taffe, Michael A; Huitron-Resendiz, Salvador; Schroeder, Richard et al. (2003) MDMA exposure alters cognitive and electrophysiological sensitivity to rapid tryptophan depletion in rhesus monkeys. Pharmacol Biochem Behav 76:141-52
Taffe, Michael A; Davis, Sophia A; Yuan, Jie et al. (2002) Cognitive performance of MDMA-treated rhesus monkeys: sensitivity to serotonergic challenge. Neuropsychopharmacology 27:993-1005

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