N-methyl-D-aspartate receptor antagonist MK-801 impairs learning but not memory fixation or expression of classical fear conditioning in goldfish (Carassius auratus).

Examined in 5 experiments the amnestic effects of the noncompetitive antagonist MK-801 on visually mediated, classic fear conditioning in goldfish (Carassius auratus). MK-801 was administered 30 min before the training session on Day 1 to look for anterograde amnestic effects, immediately after training to look for retrograde amnestic effects, and before the training or test session, or both, to look for state-dependence effects. Results show that MK-801 produced anterograde amnesia at doses that did not produce retrograde amnesia or state dependency and did not impair the expression of conditioned or unconditioned branchial suppression responses (BSRs) to the conditioned stimulus (CS). Results indicate that MK-801 disrupts the mechanism of learning of the CS–unconditioned stimulus (UCS) relation. Evidence is also presented that the learning processes that are disrupted by MK-801 occur during the initial stage of BSR conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory and N-methyl-D-aspartate receptor antagonists APV and MK-801: Memory impairments depend on familiarity with the environment, drug dose, and training duration.

Rats given N-methyl-D-aspartate (NMDA) antagonists were tested in the radial maze in spatial working memory (WM) and reference memory (RM) tasks. 16 female rats given (+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d] cycloheptene-5,10 imine (MK-801; 0.0625 mg/kg intraperitoneal/ly (ip)) before daily testing in an 8-arm WM task were impaired even after 70 days. Control rats learned quickly, were assigned to a group given MK-801 or saline, and were trained to avoid 4 of the 8 arms. MK-801 impaired this reversal learning but did not affect WM performance. 15 male rats were trained on an 8-arm WM task for 19 days and then given intracranial aminophosphonovaleric acid (APV; 33 mM), which impaired both WM and motor behavior. 24 male rats were trained for 65 days to enter 4 of 8 arms and then given intracranial APV (20 or 30 mM). WM and RM were normal in the familiar environment but were both impaired in an unfamiliar environment. Results suggest that the mnemonic effects of NMDA antagonists depend on environmental familiarity, dose, and training duration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective impairment of long-term but not short-term conditional fear by the N-methyl-D-aspartate antagonist APV.

Previous research has indicated that the competitive N-methyl-D-aspartate (NMDA) antagonist APV ({dl}-2-amino-5-phosphonovalerate) prevents the Pavlovian conditioning of fear to contextual stimuli when tested 24 hrs, but not immediately, after training. The present study investigated this differential time-dependent effect of APV on fear conditioning. Rats were given either APV or saline and presented with 3 footshocks in a distinctive chamber. Promptly after the shock, rats that had received APV exhibited a species-typical fear response: freezing. However, the freezing lasted for only a short period of time (     

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-{d}-aspartate (NMDA) receptor antagonist {dl}-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 μg/side AP5 immediately before 5 noise–footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5, because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Taste-potentiated odor conditioning: Impairment produced by infusion of an N-methyl-D-aspartate antagonist into basolateral amygdala.

Two experiments examined the effects of infusing an N-methyl-D-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate(d-APV), on taste-potentiated odor conditioning: a form of learning that is dependent on information processing in 2 sensory modalities. In Experiment 1, rats infused with d-APV were impaired in their acquisition of the potentiated learning to an odor cue. Expression of this learning and acquisition of a simple taste aversion remained intact following drug treatment. In Experiment 2, dose dependence and stereoselectivity were demonstrated for the antagonist compound. These results are consistent with previous studies demonstrating that either basolateral amygdala lesions, or treatment with NMDA antagonists, by other routes (systemic or intraventricular) produce selective deficits in taste-potentiated odor conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of MK-801 on spatial memory in homing and nonhoming pigeon breeds.

Homing pigeon breeds, the product of artificial selection on the basis of navigational and spatial ability, differ from nonhoming breeds in hippocampal size and distribution of N-methyl-{d}-aspartate (NMDA) dependent receptors. The effects of MK-801 (0.1 mg/kg administered intraperitoneally [ip]), a noncompetitive NMDA antagonist, on spatial reference memory (RM) were compared between the 2 breeds in a radial arm maze task. MK-801 disrupted the acquisition of RM in the nonhoming group but not the homing group, which was equivalent to the 2 saline-only control groups. As in previous findings with mammals, working memory was not affected by MK-801. This behavioral dissociation, coupled with differences in NMDA-dependent long-term potentiation between breeds, suggests an exceptional opportunity to investigate the role and function of the dorsomedial telencephalon region in spatial RM, through anatomical, neurochemical, and behavioral comparisons between homing and nonhoming pigeon breeds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairment of learning by localized injection of an N-methyl-D-aspartate receptor antagonist into the hyperstriatum ventrale of the domestic chick.

A restricted part of the domestic chick forebrain is critically involved in the learning process of imprinting. This region is the intermediate and medial part of the hyperstriatum ventrale (IMHV). The effect on imprinting of local injection of the N-methyl-{d}-aspartate (NMDA) receptor blocker {d}-amino-5-phosphonopentanoic acid ({d}-AP5) into the left IMHV was studied in chicks in which the right IMHV had been lesioned. The left IMHV is essential for imprinting when chicks have been lesioned in this way. Injection of ～0.7 nmol {d}-AP5 into the left IMHV significantly impaired imprinting. Injection of ～0.2 nmol {d}-AP5 into the left IMHV, or of ～0.7 nmol {d}-AP5 into the left hyperstriatum accessorium, was without significant effect on imprinting. These results suggest that NMDA receptors in the left IMHV may play an important part in this learning process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA receptor antagonist MK-801 blocks learning of conditioned stimulus-unconditioned stimulus contiguity but not fear of conditioned stimulus in goldfish (Carassius auratus L.).

The blockade of learning of Pavlovian fear conditioning by the N-methyl-D-aspartic acid (NMDA)-receptor antagonist MK-801 was examined in 166 goldfish. In previously untrained fish, MK-801 blocked learning of a light-off or a tone conditioned stimulus (CS) paired with an electrical shock unconditioned stimulus (UCS). Pretraining on the light-off CS did not affect the rate of learning of the tone CS but protected the tone learning from disruption by MK-801. Switching from the light-off to the tone CS changed the identity of the CS but not its temporal contiguity with the UCS. Pretraining consisting of pseudoconditioning of the light-off CS did not protect subsequent tone learning from blockade by MK-801. Thus, the NMDA receptor functions are necessary for learning related to the temporal contiguity of the CS and UCS but not to the identity of the CS as a cue to the occurrence of the fearful effects of the UCS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of systemic, intracerebral, or intrathecal administration on an N-methyl-D-aspartate receptor antagonist on associative morphine analgesic tolerance and hyperalgesia in rats.

A flavor paired with morphine shifted to the right the function relating morphine dose to tail-flick latencies and provoked hyperalgesic responses when rats were tested in the absence of morphine. These learned increases in nociceptive sensitivity were not mediated by alterations in tail-skin temperature. Microinjection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5) into the lateral ventricle reversed the hyperalgesic responses but spared the tolerance to morphine analgesia. By contrast, systemic administration of the noncompetitive NMDA receptor antagonist MK-801 or intrathecal infusion of AP-5 reversed the hyperalgesic responses as well as the tolerance to morphine analgesia. The results demonstrate that associatively mediated tolerance to morphine analgesia can co-occur with hyperalgesic responses and are discussed relative to learned activation of endogenous pronociceptive mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intrahippocampal infusions of a metabotropic glutamate receptor antagonist block the memory of context-specific but not tone-specific conditioned fear.

The role of metabotropic glutamate receptors (mGluRs) in the acquisition of learning and memory using fear conditioning as a behavioral model was examined. The mGluR antagonist (R,S)-α-methyl-4-carboxyphenylglycine (MCPG) was infused into the hippocampus 30 min before fear conditioning, and freezing was measured during both acquisition and retention tests. The results show that pretraining antagonism of MCPG-sensitive mGluRs in the hippocampus impaired context-specific memory for an aversive event during testing. The memory for tone-specific fear, however, remained intact despite pretraining infusion of MCPG. Treating rats with MCPG did not affect context- or tone-specific fear during acquisition. Results suggest that mGluR activation may play an important role in hippocampally mediated memory consolidation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the amnestic effects on NMDA receptor antagonist MK-801 and nitric oxide synthase inhibitors: L-NAME and L-NOARG in goldfish.

Investigations indicate that the induction of long-term potentiation (LTP) may be mediated by postsynaptic N-methyl-D-aspartate (NMDA) receptors and that the maintenance of LTP may be initiated by nitric oxide (NO), a retrograde messenger carrying signals backward from the postsynaptic to the presynaptic neuron. The present study compared amnestic effects of dizocilpine maleate (MK-801), an NMDA receptor antagonist, and nitro-L-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine (L-NOARG), nitric oxide (NO) inhibitors, in goldfish, using active-avoidance conditioning as the learning paradigm. The results showed that MK-801 and NO inhibitors produced anterograde amnesia at doses that did not impair performance processes necessary for learning to occur. Furthermore, MK-801 did not produce retrograde amnesia, whereas L-NAME did, suggesting that MK-801 impaired learning whereas NO inhibitors impaired memory consolidation and possibly also learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Yellow-nosed monkeys' (Cercopithecus ascanius whitesidei) spatial memory in a simulated foraging environment.

The spatial memory abilities of 2 yellow-nosed monkeys (Cercopithecus ascanius whitesidei), residents in a zoo, were studied in a simulated foraging environment. In the main phases of the study, trials consisted of 2 parts separated by a delay. In the 1st part, 4 food sites were baited with a highly preferred food, and the Ss were permitted to find and consume these items. During the delay, either the same 4 locations were again baited (win-stay problem) or 4 new locations were baited (win-shift problem). The monkeys were very accurate in finding food when they were reintroduced to the test enclosure after the delay, on both types of problem, and with delay intervals of up to 1 hr. In recovering food items the Ss minimized total distance travelled between the sites, which suggests that some species of monkeys, like some species of apes, may use a least-distance strategy in spatial memory tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working memory tasks in five-choice operant chambers: Use of relative and absolute spatial memories.

32 male rats were trained to nose poke into illuminated holes to perform 1 of 2 different spatial working memory tasks (relative recency or reward history) in a 5-choice operant chamber. A series of experiments indicated that choice accuracy on both tasks depended on (1) the holes' spatial separation, and (2) their relative rather than absolute positions. The results suggest that accurate choice depended on using a motor mediation strategy to turn, so as to encounter the target (correct) hole before encountering the alternative (wrong) hole. The drugs administered to the rats, d-amphetamine, scopolamine, and CGP-37849 impaired choice accuracy on these tasks, even though task performance had not appeared to depend on explicit memory for the sample responses. This suggests that parallel drug effects obtained on other operant matching- or nonmatching-to-position tasks may not have reflected truly amnesic effects of the drug treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Forgotten but not gone: Savings for pictures and words in long-term memory.

Five experiments examined the relearning of words, simple line-drawing pictures, and complex photographic pictures after retention intervals of 1 to 10 weeks. For those items that were neither recalled nor recognized, the identical item was relearned better than an unrelated control item, as measured by a recall test following relearning. This relearning advantage in recall held for all three classes of material and extended to the cross-modality case (i.e., picture–word and word–picture) and the same-referent case (i.e., two pictures of the same object). However, recognition tests of relearning failed to detect this same relearning advantage for apparently forgotten items. Taken together, these findings conflict with the existing account of savings. Most fundamental, the classic argument that relearning serves a trace-strengthening function is undermined by the observed recall-recognition contrast. An alternative explanation of savings is suggested wherein relearning assists retrieval of information, thereby affecting recall in particular. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning and performance in the radial arm maze is impaired after N-methyl-{d}-aspartate (NMDA) receptor blockade in striatal subregions.

These experiments addressed the role of striatal N-methyl-{d}-aspartate (NMDA) receptors in spatial behavior in the radial arm maze. Rats treated with the NMDA antagonist D-2-amino-5-phosphonopentanoic acid (AP-5) in the nucleus accumbens core, medial caudate, and posterior caudate were all significantly impaired in acquiring the correct spatial responses. In contrast, rats infused with AP-5 in the nucleus accumbens shell showed little impairment. When rats in all groups had learned the maze and were performing at similar levels, AP-5 had relatively little effect except in the posterior caudate group, where errors and trial times were again increased. These findings demonstrate the importance of NMDA receptor-dependent activity within the accumbens and caudate in spatial learning and performance. The neural processes necessary for adaptive spatial learning in complex environments may recruit multiple cortical systems having specialized functions, which in turn are integrated in widespread striatal regions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Infusion of neurotoxic doses of N-methyl-D-aspartate into the lateral hypothalamus in rats produces stomach erosions, hyperthermia, and a disruption in eating behavior.

The present study examined whether damage to intrinsic lateral hypothalamic (LH) neurons induced by microinfusions of N-methyl-D-aspartate (NMDA) would produce effects similar to those seen after electrolytic LH lesions. In Experiment 1, rats receiving electrolytic (1.2 mA anodal current, 10 s) LH lesions displayed motor impairments, whereas those receiving NMDA (20 μg/μl) infusions did not. Both electrolytic lesions and NMDA infusions were associated with eating deficits, hyperthermia, and gastric erosion formation 24 hr after surgery. In Experiment 2, either 20 μg/μl or 10 μg/μl NMDA destroyed LH cells and produced dose-dependent gastric mucosal erosions as well as similar increases in body temperature. These results indicate that an alteration in the acute activity of intrinsic LH neurons plays a role in the production of gastric mucosal injury and hyperthermia and lend support to other studies implicating a role of LH neurons in eating behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repetition priming for familiar and unfamiliar faces in a sex-judgment task: Evidence for a common route for the processing of sex and identity.

Repetition priming for faces was examined in a sex-judgment task given at test. Priming was found for edited, hair-removed photos of unfamiliar and familiar faces after a single presentation at study. Priming was also observed for the edited photos when study and test faces were different exemplars. Priming was not observed, however, when sex judgments were made at test to photos of complete, hair-included faces. These findings were interpreted by assuming that, for edited faces, internal features are attended, thereby activating face-recognition units that support performance. With complete faces, however, participants provided speeded judgments based primarily on the hairstyle. It is suggested that, for both familiar and unfamiliar faces, a common locus exists for the processing of the identity of a face and its sex. A single face-recognition model for the processing of familiar and unfamiliar faces is advocated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course and regional basis of Pb-induced changes in MK-801 binding: reversal by chronic treatment with the dopamine agonist apomorphine but not the D1 agonist SKF-82958

In the present study we attempted to further define the time course and regional specificity of lead (Pb)-induced changes in the NMDA receptor complex and the influence of dopaminergic system modulations on these changes. Autoradiographic measurements of alterations in MK-801 binding, as evaluated under four different activation conditions (none, spermidine, glycine, or maximal activation), were performed in medial frontal cortex, dorsal striatum, and nucleus accumbens of male rats after 2 weeks or 8 months of chronic postweaning (from 21 days of age on) exposure to 0, 50, or 150 ppm Pb acetate in drinking water. The 8-month groups also received chronic intermittent intraperitoneal injections of saline, or of the dopamine (DA) agonist apomorphine or the D1 agonist SKF-82958 2-3 times per week beginning at 60 days of age. Two weeks of 50 ppm Pb exposure resulted in small but significant increases in MK-801 binding under conditions of glycine or spermidine activation, whereas decreases were observed in response to 150 ppm under conditions of no or maximal activation in all regions. After 8 months of Pb, concentration-dependent decreases in MK-801 binding were observed across regions under all activation conditions. These effects were noted at blood Pb concentrations averaging as low as 16 microg/dl. Pb-induced decreases in MK-801 binding were either partially or fully reversed by chronic intermittent treatment with the DA agonist apomorphine but not by the D1 agonist SKF-82958, implicating D2-based mechanisms in this reversal. Combined findings from this and previous studies based on this exposure protocol indicate a Pb-induced pattern of widespread hypoglutamatergic function accompanied by increased DA function in mesolimbic systems, a pattern of changes reminiscent of those proposed to underlie schizophrenia. Such findings suggest that Pb exposure, even at current environmental levels, could be a risk factor for behavioral and/or neurological disturbances arising from imbalances of glutamate/dopamine function in mesocorticolimbic systems.     

Music training improves verbal but not visual memory: Cross-sectional and longitudinal explorations in children.

The hypothesis that music training can improve verbal memory was tested in children. The results showed that children with music training demonstrated better verbal but not visual memory than did their counterparts without such training. When these children were followed up after a year, those who had begun or continued music training demonstrated significant verbal memory improvement. Students who discontinued the training did not show any improvement. Contrary to the differences in verbal memory between the groups, their changes in visual memory were not significantly different. Consistent with previous findings for adults (A. S. Chan, Y. Ho, & M. Cheung, 1998), the results suggest that music training systematically affects memory processing in accordance with possible neuroanatomical modifications in the left temporal lobe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)