Intrahippocampal Infusion of the NMDA Receptor Antagonist AP5 Impairs Retention of an Inhibitory Avoidance Task: Protection from Impairment by Pretraining or Preexposure to the Task Apparatus

Roesler, Rafaël; Vianna, Mônica Ryff Moreira Roca; Anna, Marcia K. Sant’; Kuyven, Carlos Renato; Kruel, André Vinicius S.; Quevedo, João; Ferreira, Maria Beatriz Cardoso

doi:10.1006/nlme.1997.3810

Cited by 75 publications

(87 citation statements)

References 7 publications

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“…Perceptual learning, which can refer to a learned change in the salience and discriminability of a stimulus, is a well-documented and widespread consequence of stimulus exposure, and it profoundly alters how a subject learns about the CS during subsequent conditioning (Hall, 1991). These results are consistent with studies from spatial learning (Bannerman et al, 1995;Saucier & Cain, 1995;Saucier et al, 1996), Pavlovian contextual fear conditioning (Sanders & Fanselow, 2003) and one-trial inhibitory avoidance learning (Roesler et al, 1998), showing that the preexposure to the stimuli or actions to be learned about can determine the effects of NMDA receptor antagonism on later learning. In the case of fear extinction, the present results raise the question: What aspect of fearextinction learning do NMDA receptor antagonists normally disrupt?…”

Section: Discussionsupporting

confidence: 79%

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Chan

McNally

2009

Behavioral Neuroscience

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Six experiments studied the role of conditioned stimulus (CS) familiarity in determining the effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on fear extinction. Systemic administration of MK-801 (0.1 mg/kg) impaired initial extinction but not reextinction learning. MK-801 impaired reextinction learning when the CS was relatively novel during reextinction training but not initial extinction learning when the CS was relatively familiar during initial extinction training. A context change failed to reinstate the sensitivity of initial fear extinction learning about a relatively familiar CS to MK-801. These experiments show that CS familiarity is an important determinant of effects of MK-801 on fear extinction learning: MK-801 impaired extinction learning about novel stimuli but spared extinction learning about familiar stimuli.

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Section: Discussionsupporting

confidence: 79%

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Chan

McNally

2009

Behavioral Neuroscience

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“…Animals were placed on the platform and their latency to step down on the grid with all four paws was measured with an automatic device. In training sessions, immediately after stepping down on the grid, the animals received a 2.0-sec scrambled foot shock Jerusalinsky et al 1992;Roesler et al 1998). The shock intensity was 0.4 mA for animals given only one training session (experiments 1 and 3) and 0.2 mA for animals given two training sessions (experiment 2) (Roesler et al 1998).…”

Section: Surgerymentioning

confidence: 99%

“…In training sessions, immediately after stepping down on the grid, the animals received a 2.0-sec scrambled foot shock Jerusalinsky et al 1992;Roesler et al 1998). The shock intensity was 0.4 mA for animals given only one training session (experiments 1 and 3) and 0.2 mA for animals given two training sessions (experiment 2) (Roesler et al 1998). In test sessions, no foot shock was administered and the step-down latency (maximum 180 sec) was used as a measure of retention Jerusalinsky et al 1992;Roesler et al 1998).…”

Section: Surgerymentioning

confidence: 99%

“…The shock intensity was 0.4 mA for animals given only one training session (experiments 1 and 3) and 0.2 mA for animals given two training sessions (experiment 2) (Roesler et al 1998). In test sessions, no foot shock was administered and the step-down latency (maximum 180 sec) was used as a measure of retention Jerusalinsky et al 1992;Roesler et al 1998). In experiment 1, animals were given a single training session, followed by a retention test session 24 hr later.…”

Section: Surgerymentioning

confidence: 99%

“…As with many other tasks (Morris et al 1986;Burchuladze and Rose 1992), NMDA receptor antagonists such as AP5 are amnestic for the avoidance if injected into the hippocampus before and immediately after the training session. However, it was found recently that either pretraining or pre-exposure to the task apparatus could prevent the amnesia induced by intrahippocampal infusion of AP5 (Roesler et al 1998). This resembles the finding that both nonspatial (Saucier and Cain 1995) and spatial (Bannerman et al 1995) pretraining prevent the impairing effect of NMDA receptor antagonists on spatial recall of the Morris water maze, a task that depends on the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

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Two Time Windows of Anisomycin-Induced Amnesia for Inhibitory Avoidance Training in Rats: Protection from Amnesia by Pretraining but not Pre-exposure to the Task Apparatus

et al. 1999

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We have studied the effect of training conditions on hippocampal protein synthesis-dependent processes in consolidation of the inhibitory avoidance task. Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA foot shock, 24 hr training-test interval). Fifteen minutes before or 0, 3, or 6 hr after training, animals received a 0.8-µl intrahippocampal infusion of the protein-synthesis inhibitor anisomycin (80 µg) or vehicle (PBS, pH 7.4). The infusion of anisomycin impaired retention test performance in animals injected 15 min before and 3 hr after the training session, but not at 0 or 6 h post-training. Pretraining with a low foot shock intensity (0.2 mA) 24 hr before training, prevented the amnestic effect of anisomycin injected at 15 min before or 3 hr after training. However, simple pre-exposure to the inhibitory avoidance apparatus did not alter the amestic effects of anisomycin. The results suggest that hippocampal protein synthesis is critical in two periods, around the time of, and 3 hr after training. A prior weak training session, however, which does not itself alter step-down latencies, is sufficient to prevent the amnestic effect of anisomycin, suggesting that even if not behaviorally detectable, weak training must be sufficient to produce some lasting cellular expression of the experience.

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Inhibition of kynurenine aminotransferase II attenuates hippocampus‐dependent memory deficit in adult rats treated prenatally with kynurenine

2018

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A combination of genetic and environmental factors contributes to schizophrenia (SZ), a catastrophic psychiatric disorder with a hypothesized neurodevelopmental origin. Increases in the brain levels of the tryptophan metabolite kynurenic acid (KYNA), an endogenous antagonist of α7 nicotinic acetylcholine and NMDA receptors, have been implicated specifically in the cognitive deficits seen in persons with SZ. Here we evaluated this role of KYNA by adding the KYNA precursor kynurenine (100 mg/day) to chow fed to pregnant rat dams from embryonic day (ED) 15 to ED 22 (control: ECon; kynurenine treated: EKyn). Upon termination of the treatment, all rats received normal rodent chow until the animals were evaluated in adulthood (postnatal days 56–85). EKyn treatment resulted in increased extracellular KYNA and reduced extracellular glutamate in the hippocampus, measured by in vivo microdialysis, and caused impairments in hippocampus-dependent learning in adult rats. Acute administration of BFF816, a systemically active inhibitor of kynurenine aminotransferase II (KAT II), the major KYNA-synthesizing enzyme in the brain, normalized neurochemistry and prevented contextual memory deficits in adult EKyn animals. Collectively, these results demonstrate that acute inhibition of KYNA neosynthesis can overcome cognitive impairments that arise as a consequence of elevated brain KYNA in early brain development.

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Intrahippocampal Infusion of the NMDA Receptor Antagonist AP5 Impairs Retention of an Inhibitory Avoidance Task: Protection from Impairment by Pretraining or Preexposure to the Task Apparatus

Cited by 75 publications

References 7 publications

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Two Time Windows of Anisomycin-Induced Amnesia for Inhibitory Avoidance Training in Rats: Protection from Amnesia by Pretraining but not Pre-exposure to the Task Apparatus

Inhibition of kynurenine aminotransferase II attenuates hippocampus‐dependent memory deficit in adult rats treated prenatally with kynurenine

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