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)     

The role of telencephalic NMDA receptors in avoidance learning in goldfish (Carassius auratus).

Studies with goldfish (Carassius auratus) have suggested that N-methyl-D-aspartate (NMDA) receptors are concentrated most densely in the telencephalon, a simple structure homologous to the limbic stricture of higher vertebrates. The present study investigated the amnestic effects of microinjections of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) to the goldfish telencephalon on avoidance conditioning. Results showed that microinjections of D-AP5 before training impaired avoidance learning at doses that did not impair performance processes. High-performance liquid chromatography measurements showed that D-AP5 was detected only in the telencephalon following microinjections. Thus, D-AP5 impaired avoidance learning through its interaction with telencephalic NMDA receptors in goldfish. Furthermore, microinjections of D-AP5 to the goldfish telencephalon immediately following training did not impair memory consolidation of avoidance conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning

We have evaluated the safety of intracytoplasmic sperm injection(ICSI) procedures by using bovine zygotes. Bovine zygotes were injected with a small amount (2-3 pl) of either medium alone or medium containing polyvinylpyrrolidone (PVP) (sham-ICSI, without spermatozoon) using the same procedure as ICSI, and the subsequent in-vitro embryonic development and embryo quality (number of cells/blastocyst) were examined. Control zygotes which had not been injected were similarly evaluated after in-vitro development. The sham-ICSI of either medium alone or medium containing PVP into bovine zygotes had no harmful effects on the rate of normal fertilization and on the rate of development to hatched blastocyst stage compared with those of controls (P > 0.05). In addition, no harmful effects were observed in the number of cells per blastocyst (embryo quality). The results suggest, for the first time, that the ICSI procedures currently used for animal and human ICSI are neither detrimental to embryonic development nor detrimental to embryo quality.     

Observing response in goldfish (Carassius auratus).

In three experiments we established that goldfish make observing responses. In Experiment 1 fish were rewarded according to a mixed schedule of reinforcement with variable-interval (VI) and extinction (EXT) segments alternating randomly, each in the presence of the same exteroceptive stimulus. By striking a second target the fish in one group could produce a stimulus associated with food (S+). Fish in a second group could produce a stimulus associated with extinction (S–). Although few observing responses were made, fish apparently found aversive the S–. In Experiment 2 fish could respond on a multiple schedule of reinforcement with VI and EXT segments alternating randomly, each in the presence of a different exteroceptive stimulus or on a mixed schedule. Fish preferred the multiple side during VI segments but not during EXT segments until the predictive value of S+ and S– was reduced. In Experiment 3 fish were required to respond to produce S+ and S–. Again, fish preferred the multiple side during VI segments only. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The NMDA receptor antagonist MK-801 elicits conditioned place preference in rats

(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate, (MK-801) a potent noncompetitive antagonist of central NMDA receptors, has been hypothesized to have rewarding properties indicative of abuse potential. To test this hypothesis, the effects of MK-801 on the acquisition of a conditioned place preference and on locomotor activity were assessed and compared with d-amphetamine. Both MK-801 (0.03 and 0.1 mg/kg, SC) and d-amphetamine (1.0 mg/kg, SC) administration resulted in the acquisition of a conditioned place preference. However, while both amphetamine and the higher dose of MK-801 produced a behavioral activation during the training period the lower dose of MK-801 did not. These results suggest that MK-801, at doses that produce behavioral activation and below, is rewarding and therefore may have abuse potential.     

Serial ablations of the telencephalon and avoidance learning by goldfish (Carassius auratus).

Simultaneous bilateral ablation of the teleost telencephalon was confirmed to impair the retention, extinction, and reversal learning of a preoperatively learned instrumental avoidance response in a shuttle box. The focus of the experiment, using 30 goldfish, was on whether 2-stage serial unilateral ablations of the teleost telencephalon would ameliorate the effects seen following 1-stage bilateral ablation and whether such amelioration would be a function of S's experiences between the staged ablations. The degree of retention, relearning, and extinction of the avoidance response was not modulated by the serial ablation procedure whether or not there was interoperation retraining experience. However, reversal learning, in which the previous warning signal became the safety signal and the previous safety signal became the new warning signal, was less impaired following serial ablations than following single-stage bilateral ablation. Results are contrasted with those from experiments with mammalian Ss. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different ways of encoding geometric information by goldfish (Carassius auratus).

On the basis of results of a probe trial in 2 different experiments, K. Cheng (2005) has proposed a common mechanism for orientation in fish trained in both a maplike or relational procedure and a directly cued procedure. However, K. Cheng's model is inconsistent with previous results of goldfish (Carassius auratus) trained in these 2 tasks. Given that K. Cheng's proposal assumes that fish choose the goal by using a matching strategy in which they try to match as many properties as possible, including geometric and featural properties, future research is necessary to clarify what properties of the environmental space are codified and used for navigation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of telencephalic NO and cGMP in avoidance conditioning in goldfish (Carassius auratus).

Our previous study with N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5 suggested that NMDA receptors were involved in learning but not memory consolidation of avoidance conditioning. The present study investigated whether nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were involved in memory consolidation but not learning of avoidance conditioning in goldfish. Experiments 1 to 3 investigated amnestic and performance effects of NO inhibitor L-NAME and cGMP inhibitor LY-83583. Experiment 4 investigated whether posttraining intratelencephalic injection of NO donor SNAP ameliorated anterograde amnestic effects of pretraining NO inhibitor L-NAME. The results showed that L-NAME and LY-83583 produced significant anterograde and retrograde amnesia at doses that did not impair performance processes, and the drugs produced more severe retrograde than anterograde amnesia. Furthermore, posttraining SNAP significantly ameliorated anterograde amnestic effects of pretraining L-NAME. Thus, our previous results with D-AP5 and current results with L-NAME and LY-83583 together suggest that the NMDA receptors are involved in learning or the process that is completed during training, whereas the NO and cGMP are involved in memory consolidation or the process that is normally completed sometime following the learning experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Performance of goldfish (Carassius auratus) in patterned sequences of rewarded and nonrewarded trials.

Studied the performance of 40 goldfish in 4 experiments with patterned sequences of reward (R) and nonreward (N) for responses to a given stimulus (S3). Trials with 2 other, readily discriminable stimuli, in which response to one was always rewarded and response to the 2nd never rewarded, were interpolated in such a way that the outcome of any S3 trial could not be predicted from the events of the immediately preceding trial. The main purpose was to look for control of response to S3 based on memory of N like that found in previous work with pigeons. In Exps I and II, blocks of R and N trials with S3 were programmed, R trials in the 1st half of each session and N in the last half, or N trials in the 1st half and R in the last half. In Exp III, successive acquisition and extinction of response to S3 was studied, with the N-to-R, and R-to-N transitions either within sessions or between sessions. In Exp IV, the effects of partial and consistent reinforcement on extinction of response to S3 were compared. Results are similar in important respects to those for pigeons, as described by P. A. Couvillon et al (see record 1981-07158-001), but different in their failure to demonstrate control of performance by memory of N. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of the NMDA receptor antagonist MK-801 on short-interval timing in rats.

Effects of MK-801, an N-methyl-D-aspartate antagonist, on short-interval timing were examined using the peak-interval (PI) and PI-gap procedures. Fisher 344 rats were given daily injections of 0.025 mg/kg, 0.05 mg/kg, and 0.2 mg/kg MK-801. The main results were (a) 0.2 mg/kg MK-801 produced an immediate overestimation of the criterion time; (b) MK-801 increased peak rate of responding; (c) 0.2 mg/kg MK-801 produced an increase in variability; (d) during the PI-gap procedure, a reset pattern was observed for all rats (MK-801 and saline). Results suggest that MK-801 has at least 2 effects. First, MK-801 interferes with short-interval timing by producing an overestimation of time and a nonscalar increase in variability. Second, MK-801 increases response rate, suggesting a decrease in response inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling the effects of the NMDA receptor antagonist MK-801 on timing in rats.

The NMDA receptor antagonist MK-801 produces different effects on timing tasks. In particular, MK-801 produces an underestimation of duration when animals are tested with the differential reinforcement of low rate of responding (DRL) schedule and an overestimation of duration when animals are tested with the peak-interval (PI) procedure. The goal of this study was to develop a model-based explanation for this discrepancy. Two computer simulations were conducted via an implementation of scalar expectancy theory (SET). In Simulation 1, SET was used to provide a quantitative account of PI timing data. Simulation 2 used parameter estimates from Simulation 1 to predict effects of MK-801 on the DRL task. DRL predictions provided a close match to previous empirical data. Results of the simulations suggest that differences in the literature are likely due to inherent differences between PI and DRL tasks, rather than fundamental differences in timing. Overall, the role of NMDA receptors in timing appears to be multifaceted, impacting perception, memory, and decision processes. (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)     

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)     

The detection of pressure fluctuations, sonic audition, is the dominant mode of dipole-source detection in goldfish (Carassius auratus).

Behavioral detection of a low-frequency (40 Hz) vibratory dipole at source distances of 1.5–24 cm was measured by classically conditioned respiratory suppression in goldfish (Carassius auratus). Detection thresholds were compared across distances and before and after ablation of individual octavolateralis sensory channels. Detection thresholds, expressed in units of pressure (SPL), remained roughly constant as distance between the stimulus source and animal increased. Lateral line inactivation, using CoCl2, had no measurable effect on sensitivity, although some other results can be construed as weak evidence for a small contribution of the lateral line to dipole detection when source distances are ≤6 cm (     

Habituation in goldfish (Carassius auratus) is impaired by increased interstimulus interval, interval variability, and telencephalic ablation.

Goldfish (Carassius auratus) were fitted with electrodes and buccal catheters for monitoring EKGs and ventilations, respectively. A 2-s "light-on" stimulus was repeatedly presented to groups of fish at fixed interstimulus intervals (ISIs) of 1 or 2 min or at variable ISIs with a mean duration of 1 or 2 min. Normal fish, fish with telencephalic ablation, and fish with sham operations were compared for responsiveness and habituation to repeatedly presented stimuli. The longer the ISI, the greater the number of stimuli that were required for habituation. Increased ISI variability also decreased the rate of habituation. Furthermore, fish with telencephalic ablation had significantly slower habituation rates with both fixed and variable ISI schedules. (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)     

Localization of telencephalic regions concerned with habituation of cardiac and ventilatory responses associated with arousal in the goldfish (Carassius auratus).

54 goldfish were presented with a light-on stimulus at 2-min intervals, and their cardiac and ventilatory responses were monitored. Normal Ss, Ss with sham operations for telencephalic lesions, and Ss with bilateral electrolytic lesions of the telencephalon (anterior commissural and posterior telencephalic groups) were compared for responsiveness and habituation to regularly presented stimuli. There was no evident difference in responsiveness between the 4 groups, although 3 Ss with lesions in the regions ventralis pars dorsalis and ventralis pars ventralis gave fright responses to novel stimuli. Lesions in posterior telencephalic regions dorsalis pars centralis and ventralis pars intermedialis and at the telencephalic/diencephalic border close to the habenula caused significant impairment of habituation. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dizocilpine (MK-801) blocks tolerance to the analgesic but not to the hyperthermic effect of morphine in the rat

The effect of dizocilpine (MK-801), an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to the analgesic and hyperthermic effects of morphine was determined in the rat. Tolerance to morphine in male Sprague-Dawley rats was induced by implanting subcutaneously 6 morphine pellets during a 7-day period. Two schedules of intraperitoneal injections of MK-801 were used. In one, the drug was injected once a day, and in the other it was injected twice a day. The doses of MK-801 were 0.03, 0.1 and 0.3 mg/kg. In the treatment once a day, MK-801 blocked the development of tolerance to the analgesic effect of morphine, but there was no dose-dependent effect. In the treatment twice a day, MK-801 produced a dose-dependent inhibition of tolerance to the analgesic effect of morphine. Higher doses of MK-801 produced high mortality. MK-801 given once a day or twice a day failed to affect the tolerance to the hyperthermic effect of morphine. In both schedules of MK-801 treatment, the highest dose of MK-801 resulted in high mortality. It is concluded that MK-801 is selective in blocking the tolerance to the analgesic effect of morphine in the rat.     

N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory representation: Working memory is impaired in an unfamiliar but not in a familiar environment.

Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working-memory (WM) and reference memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perception of frequency, amplitude, and azimuth of a vibratory dipole source by the octavolateralis system of goldfish (Carassius auratus).

Goldfish (Carassius auratus) were conditioned to suppress respiration to a 40-Hz vibratory source and subsequently tested for stimulus generalization to frequency, stimulus amplitude, and position (azimuth). Animals completely failed to generalize to frequencies separated by octave intervals both lesser and greater than the CS. However, they did appear to generalize weakly to an aerial loudspeaker stimulus of the same frequency (40 Hz) after conditioning with an underwater vibratory source. Animals had a gradually decreasing amount of generalization to amplitude changes, suggesting a perceptual dimension of loudness. Animals generalized largely or completely to the same underwater source presented at a range of source azimuths. When these azimuths were presented at a transect of 3 cm, some animals did show decrements in generalization, while others did not. This suggests that although azimuth may be perceived more saliently at distances closer to a dipole source, perception of position is not immediately salient in conditioned vibratory source detection. Differential responding to test stimuli located toward the head or tail suggests the presence of perceptual differences between sources that are rostral or caudal with respect to the position of the animal or perhaps the head. (PsycINFO Database Record (c) 2011 APA, all rights reserved)