Histamine 3 receptor inverse agonist Samelisant (SUVN-G3031): Pharmacological characterization of an investigational agent for the treatment of cognitive disorders

2021 ◽  
pp. 026988112098641
Author(s):  
Ramakrishna Nirogi ◽  
Venkata R Grandhi ◽  
Rajesh B Medapati ◽  
Narender Ganuga ◽  
Vijay Benade ◽  
...  
Keyword(s):  
Object Recognition ◽  
Animal Models ◽  
Morris Water Maze ◽  
Cognitive Functions ◽  
Water Maze ◽  
Recognition Task ◽  
Inverse Agonist ◽  
Social Recognition ◽  
Morris Water Maze Task ◽  
H3 Receptors

Background: Central histamine H3 receptors are a family of presynaptic auto and heteroreceptors. Blockade of the presynaptic H3 receptors activates the downstream pathway(s) involved in the processes of learning and memory, making it a potential therapeutic option for ameliorating cognitive dysfunction. Samelisant (SUVN-G3031) is a potent and selective inverse agonist at the H3 receptors. Aim: The aim of this research is to study the effects of Samelisant in diverse animal models of cognitive functions. Methods: The effects of Samelisant on cognitive functions were studied using social recognition, object recognition and Morris water maze tasks. Neurochemical and electrophysiological effects of Samelisant were monitored using microdialysis and electroencephalography techniques. Results: Samelisant showed procognitive effects in diverse animal models of cognition at doses ranging from 0.3 to 3 mg/kg, per os ( p.o.) (social recognition and object recognition task). Samelisant significantly increased the brain acetylcholine levels in the cortex at doses of 10 and 20 mg/kg, p.o. In the Morris water maze task, combined administration of suboptimal doses of Samelisant and donepezil resulted in procognitive effects significantly larger than the either treatment. Similarly, Samelisant significantly potentiated the effects of donepezil on pharmacodynamic biomarkers of cognition i.e. acetylcholine levels in brain and neuronal theta oscillations. Conclusion: Samelisant may have potential utility in the treatment of cognitive deficits associated with hypocholinergic state.

Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud Hashemzaei ◽  
Najmeh Baratzadeh ◽  
Iraj Sharamian ◽  
Sahar Fanoudi ◽  
Mehdi Sanati ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Spatial Memory ◽  
Morris Water Maze ◽  
Spatial Learning ◽  
Water Maze ◽  
Synergistic Effects ◽  
Deionized Water ◽  
Learning Deficits ◽  
Learning Impairments ◽  
Morris Water Maze Task

Abstract Objectives H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. Methods Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 μg/μL, dissolved in saline) or O-acetyl-L-carnitine (100 μM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. Results The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. Conclusions Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

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

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.

Morris Water Maze Task—Virtual Version

2016 ◽  
Author(s):  
Eva Stening ◽  
Jonas Persson ◽  
Elias Eriksson ◽  
Lars-Olof Wahlund ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Morris Water Maze ◽  
Water Maze ◽  
Maze Task ◽  
Water Maze Task ◽  
Morris Water Maze Task

scholarly journals Differential Effects of Caffeine on Motor and Cognitive Outcomes of Penetrating Ballistic-Like Brain Injury

2019 ◽  
Vol 184 (Supplement_1) ◽  
pp. 291-300
Author(s):  
Sarah S Sanjakdar ◽  
William J Flerlage ◽  
Hyun S Kang ◽  
Douglas A Napier ◽  
Jaqueline R Dougherty ◽  
...  
Keyword(s):  
Brain Injury ◽  
Morris Water Maze ◽  
Water Maze ◽  
Right Hemisphere ◽  
Cognitive Outcome ◽  
Post Injury ◽  
Caffeine Consumption ◽  
Morris Water Maze Task ◽  
Chronic Caffeine ◽  
Caffeine Exposure

Abstract This study assessed the effect of caffeine on neurobehavioral recovery in the WRAIR penetrating ballistic-like brain injury (PBBI) model. Unilateral frontal PBBI was produced in the right hemisphere of anesthetized rats at moderate (7%-PBBI) or severe (10%-PBBI) injury levels. Animals were randomly assigned to pretreatment groups: acute caffeine (25 mg/kg CAF gavage, 1 h prior to PBBI), or chronic caffeine (0.25 g/L CAF drinking water, 30 days prior to PBBI). Motor function was evaluated on the rotarod at fixed-speed increments of 10, 15, and 20 RPM. Cognitive performance was evaluated on the Morris water maze. Acute caffeine showed no significant treatment effect on motor or cognitive outcome. Acute caffeine exposure prior to 10%-PBBI resulted in a significantly higher thigmotaxic response compared to vehicle-PBBI groups, which may indicate caffeine exacerbates post-injury anxiety/attention decrements. Results of the chronic caffeine study revealed a significant improvement in motor outcome at 7 and 10 days post-injury in the 7%-PBBI group. However, chronic caffeine exposure significantly increased the latency to locate the platform in the Morris water maze task at all injury levels. Results indicate that chronic caffeine consumption prior to a penetrating TBI may provide moderate beneficial effects to motor recovery, but may worsen the neurocognitive outcome.

scholarly journals The role of GFAP and vimentin in learning and memory

2019 ◽  
Vol 400 (9) ◽  
pp. 1147-1156 ◽  
Author(s):  
Ulrika Wilhelmsson ◽  
Andrea Pozo-Rodrigalvarez ◽  
Marie Kalm ◽  
Yolanda de Pablo ◽  
Åsa Widestrand ◽  
...  
Keyword(s):  
Object Recognition ◽  
Fear Conditioning ◽  
Morris Water Maze ◽  
Exploratory Behavior ◽  
Water Maze ◽  
Trace Fear Conditioning ◽  
Memory Extinction ◽  
Post Traumatic ◽  
Trace Fear

Abstract Intermediate filaments (also termed nanofilaments) are involved in many cellular functions and play important roles in cellular responses to stress. The upregulation of glial fibrillary acidic protein (GFAP) and vimentin (Vim), intermediate filament proteins of astrocytes, is the hallmark of astrocyte activation and reactive gliosis in response to injury, ischemia or neurodegeneration. Reactive gliosis is essential for the protective role of astrocytes at acute stages of neurotrauma or ischemic stroke. However, GFAP and Vim were also linked to neural plasticity and regenerative responses in healthy and injured brain. Mice deficient for GFAP and vimentin (GFAP−/−Vim−/−) exhibit increased post-traumatic synaptic plasticity and increased basal and post-traumatic hippocampal neurogenesis. Here we assessed the locomotor and exploratory behavior of GFAP−/−Vim−/− mice, their learning, memory and memory extinction, by using the open field, object recognition and Morris water maze tests, trace fear conditioning, and by recording reversal learning in IntelliCages. While the locomotion, exploratory behavior and learning of GFAP−/−Vim−/− mice, as assessed by object recognition, the Morris water maze, and trace fear conditioning tests, were comparable to wildtype mice, GFAP−/−Vim−/− mice showed more pronounced memory extinction when tested in IntelliCages, a finding compatible with the scenario of an increased rate of reorganization of the hippocampal circuitry.

Acquisition of a Morris water maze task is impaired during early but not late withdrawal from morphine

1996 ◽  
Vol 55 (2) ◽  
pp. 227-235 ◽  
Author(s):  
K.D. Dougherty ◽  
T.J. Walsh ◽  
S. Bailey ◽  
S. Schlussman ◽  
K. Grasing
Keyword(s):  
Morris Water Maze ◽  
Water Maze ◽  
Maze Task ◽  
Water Maze Task ◽  
Morris Water Maze Task ◽  
Late Withdrawal

Methodological Characteristics of the Use of the Morris Water Maze for Assessment of Cognitive Functions in Animals

2017 ◽  
Vol 47 (4) ◽  
pp. 484-493
Author(s):  
A. L. Ivlieva ◽  
E. N. Petritskaya ◽  
D. A. Rogatkin ◽  
V. A. Demin
Keyword(s):  
Morris Water Maze ◽  
Cognitive Functions ◽  
Water Maze
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