Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598853 (forgetting)
 3,232 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03-0.1 mg/kg) and mice (0.3-1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.
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PMID:Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716. 885 36

The endocannabinoid system has been proposed to modulate a variety of physiological processes, including those that underlie cognition. The present study tested whether this system is tonically active in learning and memory by comparing CB(1) receptor knockout mice (CB(1)(-/-)) to wild-type mice (CB(1)(+/+)) in several Morris water maze tasks. Also, the effects of three cannabinoid agonists, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), R-(+)-[2,3-dihydro-5-methyl-3[morpholinyl)methyl]-pyrrolo[1,2,3-de]-1, 4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2), and methanandamide, were evaluated in a working memory procedure. Both genotypes exhibited identical acquisition rates in a fixed platform procedure; however, the CB(1)(-/-) mice demonstrated significant deficits in a reversal task in which the location of the hidden platform was moved to the opposite side of the tank. This phenotype difference was most likely due to an increased perseverance of the CB(1)(-/-) mice in that they continued to return to the original platform location, despite being repeatedly shown the new platform location. In addition, Delta(9)-THC (ED(50) = 1.3 mg/kg), WIN 55,212-2 (ED(50) = 0.35 mg/kg), and methanandamide (ED(50) = 3.2 mg/kg) disrupted the performance of CB(1)(+/+) mice in the working memory task at doses that did not elicit motivational or sensorimotor impairment as assessed in a cued version of the task. Furthermore, doses of each drug that were maximally disruptive in CB(1)(+/+) mice were ineffective in either N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl (SR 141716A)-treated CB(1)(+/+) or CB(1)(-/-) mice. These results provide strong evidence that cannabinoids disrupt working memory through a CB(1) receptor mechanism of action, and suggest that the endocannabinoid system may have a role in facilitating extinction and/or forgetting processes.
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PMID:Evaluation of CB1 receptor knockout mice in the Morris water maze. 1202 19