Differential effects of MK-801, NMDA and scopolamine on rats learning a four-member repeated acquisition paradigm

Cohn, Jeffrey; Da, Cory-Slechta

doi:10.1097/00008877-199208000-00017

Cited by 15 publications

(2 citation statements)

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“…As noted, relatively few multiple-component repeated-acquisition studies have used rats as subjects. Many studies of repeated acquisition in rats have adopted a simplified procedure (e.g., incremental repeated acquisition) that does not include an explicit performance component (Cohn & Cory-Slechta, 1992; Paule & McMillan, 1984; Winsauer, Bixler, & Mele, 1996) or that involves between-group comparison of acquisition and performance (Baron & Moerschbaecher, 1996). Our findings with PCP emphasize the importance of within-subject analyses that involve obtaining full dose–response functions for each subject.…”

Section: Discussionmentioning

confidence: 99%

Repeated spatial acquisition: Effects of NMDA antagonists and morphine.

Galizio¹,

Keith²,

Mansfield³

et al. 2003

Experimental and Clinical Psychopharmacology

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Effects of morphine and 2 N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine and LY235959, were studied using a within-subject, repeated-acquisition/performance procedure adapted to the Morris Swim Task. In the performance component, subjects swam to a hidden platform that was always in the same location in the pool. In the acquisition component, the platform was moved to a different place for each session. Baseline training produced rapid and direct swims to the platform in the performance component and steep within-session learning curves in the acquisition component. All 3 compounds increased swim distances, escape latencies, and slowed swim speed in a dose-dependent manner, but only morphine consistently produced selective impairments on acquisition. NMDA antagonists generally affected acquisition only at doses that also disrupted performance, although phencyclidine produced selective effects in some animals. These outcomes were different than those from studies of response chains in primates, suggesting that task and species variables may be important determinants of drug effects on acquisition.

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Section: Discussionmentioning

confidence: 99%

Repeated spatial acquisition: Effects of NMDA antagonists and morphine.

Galizio¹,

Keith²,

Mansfield³

et al. 2003

Experimental and Clinical Psychopharmacology

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“…Here, we attempted to create NMDAR-associated learning deficits using MK-801, a high affinity noncompetitive NMDAR antagonist (Butelman, 1989; Shapiro and Caramanos, 1990), to determine whether preferentially inhibiting α5 subunit-containing GABA A (α 5 GABA A ) receptors would attenuate NMDA-mediated learning deficits. To test this hypothesis, we used an incremental repeated acquisition (IRA) task, which is NMDA-dependent (Cohn and Cory-Slechta, 1992), and allows for longitudinal assessment of within-subject drug effects (Bailey et al , 2010). The IRA is separated into a performance session, where the sequence of responses trained is always the same, and a learning session, where a different sequence of responses is trained each session.…”

Section: Introductionmentioning

confidence: 99%

Effects of an α5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task

Povroznik¹,

Rudy²,

Hunsberger³

et al. 2014

Behavioural Pharmacology

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N -methyl-D-aspartate receptors (NMDARs) are essential for several kinds of synaptic plasticity and play a critical role in learning and memory. Deficits in NMDAR functioning may be partially responsible for the learning and memory deficits associated with aging and numerous diseases. Administration of MK-801, a noncompetitive NMDAR antagonist, is commonly used as a preclinical model of NMDAR dysfunction. The objective of this study was to assess the effects of α5GABAA receptor inhibition on learning deficits in the incremental repeated acquisition (IRA) task induced by acute MK-801 administration. The IRA task, commonly used to examine factors that affect learning, begins with a single response and increments to progressively longer chains throughout a single session as behavior meets preset criteria. MK-801 (0.03–0.5 mg/kg, intraperitoneally), administered 10 min pretesting, produced a significant dose-dependent decrease in measures of IRA performance at doses greater than or equal to 0.25 mg/kg. The MK-801-induced deficit was attenuated after treatment with an α5GABAA receptor inverse agonist, L-655,708 (1 mg/kg, intraperitoneally). The present study provides the focus for, and supports the feasibility of, further in-depth definitive studies examining α5GABAA receptor inhibition as a suitable candidate for the attenuation of NMDAR-related deficits.

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Glutamate, learning and dementia-selection of evidence

Danysz

Archer

1994

Amino Acids

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Initial suggestions on the involvement of glutamate in memory came from electrophysiological studies on LTP that is blocked by NMDA-antagonists. Then Morris and colleagues (1986) provided the first evidence that icv infusion of the competitive NMDA antagonist 2-amino-5-phosphonovaleric acid (APV) to rats, inhibits both LTP in vivo and spatial learning in a Morris water maze. This was followed by a great amount of evidence confirming the initial finding in various learning tasks. The present paper is devoted to critical review of the literature focusing on the following problems: which glutamate receptors are involved?, in which tests NMDA antagonists inhibit learning?; which types of memory are affected?; which brain structures are involved?; do NMDA receptor antagonists invariably impair learning?; is the effect of NMDA receptors antagonists on learning specific?; does the stimulation of NMDA receptors result in cognitive enhancement?.

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Differential effects of MK-801, NMDA and scopolamine on rats learning a four-member repeated acquisition paradigm

Cited by 15 publications

References 0 publications

Repeated spatial acquisition: Effects of NMDA antagonists and morphine.

Repeated spatial acquisition: Effects of NMDA antagonists and morphine.

Effects of an α5GABAA inverse agonist on MK-801-induced learning deficits in an incremental repeated acquisition task

Glutamate, learning and dementia-selection of evidence

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