Differential muscarinic and NMDA contributions to visuo-spatial paired-associate learning in rhesus monkeys

Taffe, Michael A.; Weed, Michael R.; Gutierrez, Tannia; Davis, Sophia A.; Gold, Lisa

doi:10.1007/s00213-001-0954-5

Cited by 66 publications

(74 citation statements)

References 45 publications

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“…In brief, the monkey was required to learn and remember the association of a visual stimulus and a location on the touch screen (Supplementary Figure 1; Taffe et al, 2002b). For a given trial there were either two, three, or four stimulus/ location pairs to remember.…”

Section: Behavioral Procedures: Vspalmentioning

confidence: 99%

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Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains

Weed

Bookbinder

Polino

et al. 2015

Neuropsychopharmacol

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Antidepressant activity of N-methyl-D-aspartate (NMDA) receptor antagonists and negative allosteric modulators (NAMs) has led to increased investigation of their behavioral pharmacology. NMDA antagonists, such as ketamine, impair cognition in multiple species and in multiple cognitive domains. However, studies with NR2B subtype-selective NAMs have reported mixed results in rodents including increased impulsivity, no effect on cognition, impairment or even improvement of some cognitive tasks. To date, the effects of NR2B-selective NAMs on cognitive tests have not been reported in nonhuman primates. The current study evaluated two selective NR2B NAMs, CP101,606 and BMT-108908, along with the nonselective NMDA antagonists, ketamine and AZD6765, in the nonhuman primate Cambridge Neuropsychological Test Automated Battery (CANTAB) list-based delayed match to sample (list-DMS) task. Ketamine and the two NMDA NR2B NAMs produced selective impairments in memory in the list-DMS task. AZD6765 impaired performance in a nonspecific manner. In a separate cohort, CP101,606 impaired performance of the nonhuman primate CANTAB visuo-spatial Paired Associates Learning (vsPAL) task with a selective impairment at more difficult conditions. The results of these studies clearly show that systemic administration of a selective NR2B NAM can cause transient cognitive impairment in multiple cognitive domains.

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Section: Behavioral Procedures: Vspalmentioning

confidence: 99%

“…Stimuli changed after correct trials or after six failed attempts. As with previous studies, a session consisted of 10 trials at each difficulty level presented in an ascending order of difficulty (Taffe et al, 2002b).…”

Section: Behavioral Procedures: Vspalmentioning

confidence: 99%

Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains

Weed

Bookbinder

Polino

et al. 2015

Neuropsychopharmacol

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“…BMS required the animal to extract raisins from holes in a transparent polycarbonate board and RTT required the animal to retrieve pellets from a rotating turntable. Comprehensive descriptions of the individual tasks and the procedural details have been previously reported (Taffe et al 2002c;Taffe 2004;Taffe et al 2004;Weed et al 1999); however a brief description follows. The time required to train the tasks for these particular subjects was highly consistent with data presented in those prior methodological reports.…”

Section: Apparatusmentioning

confidence: 99%

“…Dopaminergic manipulation was conducted via acute challenge with the D 1 -like antagonist SCH23390 and the D 2 -like antagonist raclopride. Monkeys were assessed on tests that have been previously shown to be selectively affected or differentially sensitive to a number of acute pharmacological challenges in rhesus monkeys including cholinergic (Katner et al 2004a;Taffe et al 1999;Taffe et al 2002c), glutamatergic (Taffe et al 2002a;Taffe et al 2002c) and serotonergic (Taffe et al 2002b;Taffe et al 2003b) manipulations. Performance is also affected by neurotropic viral infection Weed et al 2004), alcohol consumption (Katner et al 2004b), the aging process (Taffe et al 2003a) and experimental changes in motivational status (Taffe 2004;Weed et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys

et al. 2006

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Rationale-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 D 1 -like and D 2 -like receptor subtypes play in complex brain functions.Methods-Monkeys (N=6) were trained on cognitive tests adapted from a human neuropsychological assessment battery (CANTAB; CAmbridge Neuropsychological Test Automated Battery). The battery included tests of spatial working memory (self-ordered spatial search task, SOSS), 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. Effects of the dopamine D 2 -like antagonist raclopride (10-56 μg/kg, i.m.) and the D 1 -like antagonist SCH23390 (SCH; 3.2-56 μg/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 D 2 -like over D 1 -like receptors to both spatial working memory and object-location associative memory.

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“…The monkeys were approximately 7-8 years of age (i.e., young adult) and weighed 8-12 kg at the beginning of the study. The monkeys had previously been trained on components of a behavioral test battery Taffe, 2004) and had participated in prior acute drug challenge studies with ketamine (Taffe et al, 2002b;Taffe et al, 2002c), scopolamine (Taffe et al, 2002c), nicotine and mecamylamine (Katner et al, 2004), and Δ 9 -tetrahydrocannabinol; these drugs were administered at least 3 months prior to the current study. The animals' diet was restricted 5 days per week to ensure consistent behavioral responding in the test battery while maintaining adequate growth rates.…”

Section: Animalsmentioning

confidence: 99%

Controlled and Behaviorally Relevant Levels of Oral Ethanol Intake in Rhesus Macaques Using a Flavorant‐Fade Procedure

Katner

Flynn

Huben

et al. 2004

Alcoholism Clin & Exp Res

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Background: Flavorant‐fading procedures can initiate and maintain oral ethanol intake in rodents. The present study developed a similar procedure to achieve controlled and behaviorally relevant levels of ethanol intake in monkeys.Methods: Male rhesus macaques (N= 13) were initially given the opportunity to consume 0.5 g/kg of a 1% (w/v) ethanol plus 4% (w/v) Tang solution in 1‐hr limited‐access sessions without the requirement of an operant response. Once consumption was stable at a particular concentration (%) and/or amount (g/kg), animals were given access to higher concentrations and/or amounts of ethanol. Animals were tested on a bimanual motor skill (BMS) task 20 and 90 min after consumption to assess behavioral impairment. Blood alcohol levels (BALs) were assessed after a session in which animals had the opportunity to consume up to 3.0 g/kg of 6% (w/v) ethanol.Results: The gradual fading up of higher concentrations and amounts of ethanol resulted in controlled and robust levels (>2.0 g/kg) of ethanol intake in half of the subjects. Increasing the concentration of the sweetener from 4 to 6% (w/v) was effective in initiating consumption in three animals. Two monkeys required the additional step of presenting the increased‐sweetener solutions after a meal (postprandial consumption) to initiate significant ethanol intake. Animals were significantly impaired on the BMS task after consumption of 2.0, 2.5, and 3.0 g/kg of ethanol. Individual consumption ranging from 0.8 to 3.0 g/kg of ethanol produced BALs of 18 to 269 mg/dl.Conclusions: The flavorant‐fading procedure was effective in producing behaviorally relevant levels of ethanol consumption in rhesus macaques. This model facilitated a randomized‐dose procedure to determine the behavioral effects of 0.5 to 3.0 g/kg of ethanol. This procedure therefore is of significant utility in determining behavioral or physiologic effects of specific doses of consumed ethanol in monkeys.

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Differential muscarinic and NMDA contributions to visuo-spatial paired-associate learning in rhesus monkeys

Cited by 66 publications

References 45 publications

Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains

Negative Allosteric Modulators Selective for The NR2B Subtype of The NMDA Receptor Impair Cognition in Multiple Domains

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys

Controlled and Behaviorally Relevant Levels of Oral Ethanol Intake in Rhesus Macaques Using a Flavorant‐Fade Procedure

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