Spatial learning deficit after NMDA receptor blockade and state-dependency

Bd, Kretschmer; Fink, Susan E.

doi:10.1097/00008877-199907000-00009

Cited by 16 publications

(11 citation statements)

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“…Furthermore, the effects of clonidine on performance in an eight-arm radial maze were determined in rats after MK-801 treatment. The discrete-trial delayed alternation task and the radial-arm maze were chosen since numerous studies have demonstrated decrements in memory after hippocampal damage or NMDA receptor antagonist administration Dudchenko, 2001;Kretschmer and Fink, 1999;Moghaddam et al, 1997). In the present studies, the doses of clonidine and MK-801, and the timing of drug administration were similar to the doses and drug administration schedules used in previous studies of spatial memory involving either drug (Ammassari-Teule et al, 1991;Bardgett et al, 2003;Jentsch and Anzivino, 2004).…”

Section: Introductionmentioning

confidence: 90%

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Bardgett

Points

Ramsey-Faulkner

et al. 2007

Neuropsychopharmacol

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Spatial memory impairments observed in Alzheimer's disease and schizophrenia have been attributed to many factors, including glutamate hypofunction and reduced hippocampal volume. Clonidine, a non-specific a 2 adrenergic receptor agonist, improves spatial memory in animals treated with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine; however, its effects on memory deficits produced by other NMDA antagonists or hippocampal damage have not been fully characterized. The purpose of this study was to determine if clonidine could alleviate memory deficits produced by the NMDA antagonist, MK-801, or by excitotoxic hippocampal damage. In the first phase of the study, male rats were pretreated with clonidine (0.01 or 0.05 mg/kg) or saline, and treated with MK-801 (0.1 mg/kg) or saline prior to discrete-trial delayed alternation or radial-arm maze testing. MK-801 impaired delayed alternation performance and increased the number of arm revisits in the radial-arm maze. Clonidine pretreatment significantly alleviated these druginduced deficits. In the second phase of the study, excitotoxic damage was produced in the dorsal hippocampus with NMDA. Hippocampal damage produced a significant impairment in the delayed alternation task, yet pretreatment with clonidine did not alleviate this damage-induced deficit. Taken together, the data indicate that clonidine alleviates memory impairments produced by glutamate hypofunction, but not by hippocampal damage. This caveat may be important in designing treatments for memory disorders not linked to a single pathophysiological mechanism.

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Section: Introductionmentioning

confidence: 90%

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Bardgett

Points

Ramsey-Faulkner

et al. 2007

Neuropsychopharmacol

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“…However, Nakagawa and Iwasaki (1996) did not find MK-801-induced state-dependency effects in passive avoidance learning, and Kretschmer and Fink (1999) also found no state-dependency effects of MK-801 in an eight-arm radial-maze learning task. Passive avoidance and spatial learning in a radial maze are complex associative learning tasks which appear to depend less heavily on basal ganglia functions but rather on glutamatergic transmission in the hippocampus and related areas (Munoz and Grossman 1981;Hagan et al 1983;Morris et al 1986;Stubley-Weatherly et al 1996).…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 85%

“…Thus, if this categorization of Kretschmer and Fink (1999) proves to be correct, this could explain nicely why some authors find state-dependency effects of NMDAreceptor antagonists and others do not, and would help to resolve the apparent inconsistencies in the literature.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 89%

“…An intriguing hypothesis to explain the somewhat inconsistent results on the state-dependency-inducing effects of NMDA-receptor antagonists has recently been offered by Kretschmer and Fink (1999). These authors propose that whether MK-801 or related drugs make learning and recall state dependent depends on the type of learning task and the type of learning involved.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

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Blockade of behavioral sensitization by MK-801: fact or artifact?

Tzschentke

Schmidt

2000

Psychopharmacology

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The studies reviewed herein have produced results both consistent with and in contradiction to the view that MK-801 and related drugs block behavioral plasticity, and the debate about how exactly MK-801 and related drugs interact with other drugs in sensitization experiments is still in full swing. What seems crucial for future studies relating to this subject is a careful experimental design to reduce the number of potential interpretations of the findings.

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“…For example, several authors have found that lesions causing spatial working memory deficits also cause increased movement speed. Ventral hippocampal lesions (Bannerman et a!., 1999), cholinergic basal forebrain lesions (Waite et a!., 1995), and NMDA receptor antagonism (Kretschmer & Fink, 1999) impair both spatial working memory and cause an increase in movement speed. Pleskacheva et a!.…”

Section: Attenhonalmentioning

confidence: 99%

A neural model of cortico-cerebellar interactions during attentive imitation and predictive learning of sequential handwriting movements

Grossberg

Paine

2000

Neural Networks

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Much sensory-motor behavior develops through imitation, as during the learning of handwriting by children. Such complex sequential acts are broken down into distinct motor control synergies, or muscle groups, whose activities overlap in time to generate continuous, curved movements that obey an inverse relation between curvature and speed. How are such complex movements learned through attentive imitation? Novel movements may be made as a series of distinct segments, but a practiced movement can be made smoothly, with a continuous, often bellshaped, velocity profile. How does learning of complex movements transform reactive imitation into predictive, automatic performance? A neural model is developed which suggests how parietal and motor cortical mechanisms, such as difference vector encoding, interact with adaptivelytimed, predictive cerebellar learning during movement imitation and predictive performance. To initiate movement, visual attention shifts along the shape to be imitated and generates vector movement using motor cortical cells. During such an imitative movement, cerebellar Purkinje cells with a spectrum of delayed response profiles sample and Jearn the changing directional information and, in turn, send that learned information back to the cortex and eventually to the muscle synergies involved. If the imitative movement deviates from an attentional focus around a shape to be imitated, the visual system shifts attention, and may make an eye movement, back to the shape, thereby providing corrective directional information to the arm movement system. This imitative movement cycle repeats until the corticocerebellar system can accurately drive the movement based on memory alone. A cortical working memory buffer transiently stores the cerebellar output and releases it at a variable rate, allowing speed scaling of learned movements which is limited by the rate of cerebellar memory readout. Movements can be learned at variable speeds if the density of the spectrum of delayed cellular responses in the cerebellum varies with speed. Learning at slower speeds facilitates learning at faster speeds. Size can be varied after learning while keeping the movement duration constant (isochrony). Context-effects arise from the overlap of cerebellar memory outputs. The model is used to simulate key psychophysical and neural data about learning to make curved movements, including a decrease in writing time as learning progresses; generation of unimodal, bell-shaped velocity profiles for each movement synergy; size and speed scaling with preservation of the letter shape and the shapes of the velocity profiles; an inverse relation between curvature and tangential velocity; and a Two-Thirds Power Law relation between angular velocity and curvature.

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Spatial learning deficit after NMDA receptor blockade and state-dependency

Cited by 16 publications

References 0 publications

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

The Effects of Clonidine on Discrete-Trial Delayed Spatial Alternation in Two Rat Models of Memory Loss

Blockade of behavioral sensitization by MK-801: fact or artifact?

A neural model of cortico-cerebellar interactions during attentive imitation and predictive learning of sequential handwriting movements

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