Impairment of spontaneous alternation performance by an nmda antagonist: attenuation with non-NMDA treatments

doi:10.1016/0163-1047(92)90952-Z

Behavioral and Neural Biology

Volume 58, Issue 1, July 1992, Pages 69-71

https://doi.org/10.1016/0163-1047(92)90952-Z Get rights and content

N-Methyl-d-aspartate (NMDA) receptor antagonists disrupt learning on a variety of tasks. Previous findings indicate that glucose, naloxone, and physostigmine ameliorate learning deficits produced by several treatments. The present experiment examines whether these agents also reverse the amnestic effects of NMDA receptor blockade. Mice were tested for spontaneous alternation performance in a Y-maze. The animals received either saline or the NMDA antagonist, NPC 12626 (35 mg/kg, IP), 50 min prior to testing and received an additional injection of saline, glucose, naloxone, or physostigmine 30 min prior to testing. NPC 12626 significantly decreased alternation scores. Glucose (250 mg/kg), physostigmine (0.01 mg/kg), and naloxone (1 mg/kg) reversed the effects of NPC 12626. Thus, impairments of learning after NMDA receptor blockade share with other anmestic conditions the susceptibility to attenuation by glucose, naloxone, and physostigmine.

References (10)

FlintR.S. et al.
Monoamine, amino acid and cholinergic interactions in slices of rat cerebral cortex
Brain Research Bulletin
(1985)
FloodJ.F. et al.
Antagonism of endogenous opioids modulates memory processing
Brain Research
(1987)
MarkramH. et al.
Acetylcholine potentiates response to N-methyl-d-aspartate in the rat hippocampus
Neuroscience Letters
(1990)
WalkerD.L. et al.
Effects of the novel NMDA antagonist, NPC 12626, on long-term potentiation, learning and memory
Brain Research
(1991)
WardL. et al.
Effects of the NMDA antagonists CPP and MK-801 on radial arm maze performance in rats
Pharmacology, Biochemistry, and Behavior
(1990)

There are more references available in the full text version of this article.

Cited by (33)

D-Cycloserine reverses scopolamine-induced object and place memory deficits in a spontaneous recognition paradigm in rats
2019, Pharmacology Biochemistry and Behavior
Citation Excerpt :
First, DCS has been reported fail to ameliorate scopolamine-induced memory impairment (Pitkänen et al., 1995; Rupniak et al., 1992). Second, AChE inhibitors reverse NMDA receptor antagonist-induced memory deficits (Csernansky et al., 2005; Patel et al., 1998; Walker and Gold, 1992). Considering these studies tested the effect of drugs with systemic injection, it might be better to investigate the mechanism of cholinergic and glutamatergic interaction by focusing on more specific brain areas.
d-Cycloserine (DCS) is a partial agonist of the glutamatergic N-methyl-d-aspartate (NMDA) receptor-associated glycine site, and it prevents the amnesic effects of the muscarinic receptor antagonist scopolamine in various memory tests in rodents. In the present study, we tested the hypothesis that DCS has anti-amnesic effects in scopolamine-induced deficits using spontaneous object recognition and place recognition tests. In both tests, scopolamine (0.5 mg/kg, i.p.) was systemically administered 60 min prior to testing, while DCS (7.5, 15, 30 mg/kg, i.p.) was administered 30 min before testing, which consisted of a sample phase (5 min), a delay interval (15 min) and a test phase (2 min). DCS treatment reversed scopolamine-induced deficits in discriminatory behavior during the test phase. However, DCS did not affect decreased object exploration itself or increased thigmotaxis in the open-field arena induced by scopolamine. These results support our hypothesis and suggest differential contributions of glutamatergic-cholinergic system interactions to recognition memory and non-mnemonic exploratory behaviors.
Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome
2008, Neurobiology of Learning and Memory
Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer’s disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22–25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 μg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.
Glutamate receptor function in learning and memory
2003, Behavioural Brain Research
The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task.
Site-selective N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonists produce distinct effects in rats performing complex discriminations
2002, Neurobiology of Learning and Memory
Glutamate receptor-dependent neural plasticity is thought to be implicated in memory processes. Ionotropic N-methyl-d-aspartate- (NMDA) sensitive and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- (AMPA) sensitive glutamate receptors have been particularly studied for their role in synaptic plasticity. Drugs can alter AMPA and NMDA receptor neurotransmission by competing for the glutamate site or other sites on these receptor proteins. Variants of the protein subunits forming AMPA and NMDA heteromers contribute to the complexity of pharmacological activity at these receptors. The NMDA receptor has numerous modulatory centers, including the glycine binding site, NR2B protein specific binding site, and an intrachannel (PCP) binding site. In this study, the accuracy and rate of rats performing under a Fixed Consecutive Number (FCN) operant task were measured after administrations of site-selective AMPA and NMDA receptor modulators. Test compounds included two glycine site NMDA agonists [(+)HA 966 and d-cycloserine], two NR2-B site NMDA antagonists (eliprodil and ifenprodil), an NMDA channel blocking antagonist (MK 801), and a competitively acting AMPA receptor antagonist (NBQX). The accuracy of FCN performance was not affected by response-rate-altering doses of (+) HA 966, d-cycloserine, eliprodil, ifenprodil, or NBQX. MK 801, on the other hand, reduced performance accuracy at several doses. These results are consistent with earlier studies suggesting that AMPA antagonists minimally affect working memory and that glycine and NR2B protein-specific modulatory sites may have advantages as targets for the development of medications intended to alter NMDA receptor-mediated transmission.
The neurobiological basis of spontaneous alternation
2002, Neuroscience and Biobehavioral Reviews
When placed in a T-maze, rats or mice possess a strong tendency of alternating arm choices on successive trials. The exploration of novel environmental stimuli is dependent on the integrity of limbic and non-limbic pathways, including the basal forebrain, the hippocampus, the thalamus, the prefrontal cortex, and the dorsal striatum, as well as the vestibular system and cerebellum. Neurochemical pathways using acetylcholine, gamma-amino-butyric acid, and dopamine in the septum and hippocampus have been implicated in the exploration of novel maze arms. In addition to the delineation of interactions between neurotransmitters, the spontaneous alternation test is sensitive to the consequences of normal and pathological aging.
Glucose enhancement of a facial recognition task in young adults
2000, Physiology and Behavior
Numerous studies have reported that glucose administration enhances memory processes in both elderly and young adult subjects. Although these studies have utilized a variety of procedures and paradigms, investigations of both young and elderly subjects have typically used verbal tasks (word list recall, paragraph recall, etc.). In the present study, the effect of glucose consumption on a nonverbal, facial recognition task in young adults was examined. Lemonade sweetened with either glucose (50 g) or saccharin (23.7 mg) was consumed by college students (mean age of 21.1 years) 15 min prior to a facial recognition task. The task consisted of a familiarization phase in which subjects were presented with “target” faces, followed immediately by a recognition phase in which subjects had to identify the targets among a random array of familiar target and novel “distractor” faces. Statistical analysis indicated that there were no differences on hit rate (target identification) for subjects who consumed either saccharin or glucose prior to the test. However, further analyses revealed that subjects who consumed glucose committed significantly fewer false alarms and had (marginally) higher d-prime scores (a signal detection measure) compared to subjects who consumed saccharin prior to the test. These results parallel a previous report demonstrating glucose enhancement of a facial recognition task in probable Alzheimer's patients; however, this is believed to be the first demonstration of glucose enhancement for a facial recognition task in healthy, young adults.

View all citing articles on Scopus

¹: This research was supported by research grants from the National Science Foundation (BNS-9012239), Office of Naval Research (N0001489-J-1216), and the National Institute on Aging (AG 07648). D.L.W. is a predoctoral trainee on an NIMH training grant in behavioral neuroscience (5-T32-MH18411). NPC 12626 was generously supplied by Nova Pharmaceutical Corporation (Baltimore, MD).

View full text

Brief reportImpairment of spontaneous alternation performance by an nmda antagonist: attenuation with non-NMDA treatments

Brain Research Bulletin

Brain Research

Neuroscience Letters

Brain Research

Pharmacology, Biochemistry, and Behavior

Brief report
Impairment of spontaneous alternation performance by an nmda antagonist: attenuation with non-NMDA treatments