Contrasting effects of acute and chronic treatments with ketamine on inhibitory avoidance and escape latency in the elevated-t-maze

AbstractExtinction memory destabilized by recall is restabilized through mTOR-dependent reconsolidation in the hippocampus, but the upstream pathways controlling these processes remain unknown. Hippocampal NMDARs drive local protein synthesis via mTOR signaling and may control active memory maintenance. We found that in adult male Wistar rats, intra dorsal-CA1 administration of the non-subunit selective NMDAR antagonist AP5 or of the GluN2A subunit-containing NMDAR antagonist TCN201 after step down inhibitory avoidance (SDIA) extinction memory recall impaired extinction memory retention and caused SDIA memory recovery. On the contrary, pre-recall administration of AP5 or of the GluN2B subunit-containing NMDAR antagonist RO25-6981 had no effect on extinction memory recall or retention per se but hindered the recovery of the avoidance response induced by post-recall intra-CA1 infusion of the mTOR inhibitor rapamycin. Our results indicate that GluN2B-containing NMDARs are necessary for extinction memory destabilization whereas GluN2A-containing NMDARs are involved in its restabilization, and suggest that pharmacological modulation of the relative activation state of these receptor subtypes around the moment of extinction memory recall may regulate the dominance of extinction memory over the original memory trace.

Download Full-text

Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats

Scientific Reports ◽

10.1038/s41598-021-93861-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ning Zhang ◽

Wei Zhao ◽

Zhen-Jie Hu ◽

Sheng-Mei Ge ◽

Yan Huo ◽

...

Keyword(s):

Vitamin C ◽

Escape Latency ◽

Morris Water Maze Test ◽

Protective Mechanism ◽

High Dose ◽

Maze Test ◽

Tnf Α ◽

Histopathologic Changes ◽

High Dose Vitamin ◽

Necrosis Factor

AbstractSepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

Download Full-text

Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats

Brain Research ◽

10.1016/0006-8993(89)91161-x ◽

1989 ◽

Vol 493 (2) ◽

pp. 258-268 ◽

Cited By ~ 20

Author(s):

Catherine A. Cornwell-Jones ◽

Michael W. Decker ◽

Julia W. Chang ◽

Barry Cole ◽

Kimberly M. Goltz ◽

...

Keyword(s):

Avoidance Learning ◽

Inhibitory Avoidance ◽

Inhibitory Avoidance Learning

Download Full-text

Impairment in the aversive memory of mice in the inhibitory avoidance task but not in the elevated plus maze through intra-amygdala injections of histamine

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2015.05.023 ◽

2015 ◽

Vol 135 ◽

pp. 237-245 ◽

Cited By ~ 3

Author(s):

Fernanda Daher ◽

Rosana Mattioli

Keyword(s):

Elevated Plus Maze ◽

Inhibitory Avoidance ◽

Avoidance Task ◽

Inhibitory Avoidance Task ◽

Plus Maze

Download Full-text

Inhibitory avoidance deficit following short-term adrenalectomy in the rat: The role of adrenal catecholamines

Behavioral and Neural Biology ◽

10.1016/s0163-1047(83)90910-x ◽

1983 ◽

Vol 39 (2) ◽

pp. 241-258 ◽

Cited By ~ 68

Author(s):

J. Borrell ◽

E.R. De Kloet ◽

D.H.G. Versteeg ◽

B. Bohus

Keyword(s):

Inhibitory Avoidance ◽

Short Term ◽

Avoidance Deficit

Download Full-text

NF-κB transcription factor is required for inhibitory avoidance long-term memory in mice

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2005.04126.x ◽

2005 ◽

Vol 21 (10) ◽

pp. 2845-2852 ◽

Cited By ~ 65

Author(s):

Ramiro Freudenthal ◽

Mariano M. Boccia ◽

Gabriela B. Acosta ◽

Mariano G. Blake ◽

Emiliano Merlo ◽

...

Keyword(s):

Transcription Factor ◽

Inhibitory Avoidance ◽

Long Term Memory ◽

Term Memory

Download Full-text

5-HT2A receptor activation in the dorsolateral septum facilitates inhibitory avoidance in the elevated T-maze

Behavioural Brain Research ◽

10.1016/j.bbr.2011.08.044 ◽

2012 ◽

Vol 226 (1) ◽

pp. 50-55 ◽

Cited By ~ 14

Author(s):

D.C. de Paula ◽

A.S. Torricelli ◽

M.R. Lopreato ◽

J.O.G. Nascimento ◽

M.B. Viana

Keyword(s):

Inhibitory Avoidance ◽

Receptor Activation

Download Full-text

MORRIS WATER MAZE – A BENCH MARK TEST FOR LEARNING AND MEMORY DISORDERS IN ANIMAL MODELS: A REVIEW

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i5.24292 ◽

2018 ◽

Vol 11 (5) ◽

pp. 25

Author(s):

Ch Venkataramaiah ◽

G Swathi ◽

W Rajendra

Keyword(s):

Animal Models ◽

Learning And Memory ◽

Morris Water Maze ◽

Water Maze ◽

Escape Latency ◽

Bench Mark ◽

Spatial Learning And Memory ◽

Preclinical Research ◽

Escape Route ◽

Laboratory Rats

The morris water maze (MWM) was developed by morris as a device to investigate spatial learning and memory in laboratory rats. MWM has become one of the most frequently used laboratory tools in behavioral neuroscience. The MWM task has been often used in the validation of rodent models for neurocognitive disorders (e.g., Parkinson, Alzheimer, Epilepsy, and Schizophrenia), and the evaluation of possible neurocognitive treatments. It is also being used to assess the properties of established potential antipsychotics in animal models of Schizophrenia. The MWM task requires rats to find a hidden platform in a large, circular pool of water that is colored opaque with powdered non-fat milk (or) non-toxic tempera paint where they must swim to the hidden platform. Because they are in the opaque water, the animals cannot see the platform and cannot rely on scent to find the escape route. Instead, they must rely on extra-maze cues. The behavior of rat can be evaluated by analyzing the different parameters such as escape latency, swim speed, and path length, and probe trail. The purpose of this review is to briefly describe procedural aspects, interpretational difficulties of data and advantages of MWM. This paradigm has become a benchmark test for learning and memory difficulties in animal models and preclinical research in general.

Download Full-text