SLV330, a cannabinoid CB1 receptor antagonist, ameliorates deficits in the T-maze, object recognition and Social Recognition Tasks in rodents

Autor: E. Hissink, Jos Prickaerts, Josephus H. M. Lange, L. Heijink, Kruse Cornelis G, J. Wijnen, M. van Drimmelen, E. Andriambeloson, M. de Haan, Sven Akkerman, N.M.W.J. de Bruin
Přispěvatelé: Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience
Rok vydání: 2010
Předmět:
Male
Nicotine
Aging
medicine.drug_class
Cognitive Neuroscience
Scopolamine
Experimental and Cognitive Psychology
Neuropsychological Tests
T-maze Continuous Alternation Task (T-CAT)
SLV330
Random Allocation
Mice
Behavioral Neuroscience
Receptor
Cannabinoid
CB1
medicine
Animals
Donepezil
Rats
Wistar
Maze Learning
Episodic memory
Nootropic Agents
Object Recognition Task (ORT)
Memory Disorders
Sulfonamides
MK-801
Learning Disabilities
Cannabinoid CB1 receptor (CB1R) antagonist
Working memory
Antagonist
Muscarinic antagonist
Recognition
Psychology
T-maze
Social Recognition Task (SRT)
Rats
Mice
Inbred C57BL
Dizocilpine
Disease Models
Animal
Memory
Short-Term
Social Perception
Acetylcholinesterase inhibitor
Pattern Recognition
Physiological
Pyrazoles
Psychology
Neuroscience
Time delay
medicine.drug
Zdroj: Neurobiology of Learning and Memory, 93(4), 522-531. Elsevier Science
ISSN: 1074-7427
Popis: Cannabinoid CB1 receptor (CB1R) signaling has been suggested to play an important role in the regulation of memory and cognition. In the present study, our aim was to investigate whether the CB1R antagonist SLV330 (doses ranging from 0.3 to 10 mg/kg, given orally, p.o.) could ameliorate impairments in distinct aspects of cognition using different disruption models in both mice and rats. Effects of SLV330 were tested on working memory deficits in the T-maze Continuous Alternation Task (T-CAT) in mice; episodic memory deficits in the Object Recognition Task (ORT) and Social Recognition Task (SRT) in rats. The acetylcholinesterase inhibitor (AChEI) donepezil (Aricept®, approved for symptomatic treatment of Alzheimer’s disease) and nicotine were used as reference compounds. SLV330 markedly improved aging and scopolamine-induced memory deficits in the T-CAT in mice with a lowest effective dose (LED) of 1 mg/kg p.o., while reversing the cognitive dysfunction induced by the N-methyl- d -aspartate (NMDA) antagonist dizocilpine (MK-801) only at the middle dose of 3 mg/kg. In the ORT, we have found that combined administration of subthreshold doses of SLV330 (1 mg/kg, p.o.) and the AChEI donepezil (0.1 mg/kg, p.o.), that had no discernable effects on performance when given alone, enhanced memory performance in Wistar rats with deficits induced by the muscarinic antagonist scopolamine, suggestive of additive synergistic effects of SLV330 and donepezil on cognitive impairment. Finally, SLV330 was found to have cognition enhancing properties in a time delay paradigm in the SRT at a LED dose of 3 mg/kg (p.o.). In conclusion, the CB1R antagonist SLV330 was found to clearly improve memory in several preclinical models for cognitive impairment.
Databáze: OpenAIRE
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