Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The observations that the cannabinoid(1)(CB(1)) receptor antagonist/inverse agonist, rimonabant, and the selective noncompetitive inhibitor of acetylcholinesterase (AChE), donepezil, improve performance in a variety of animal memory models, suggest that these neurochemical systems play integral roles in cognition. The present study tested whether each of these agents administered alone or in combination will prolong the duration of spatial memory. Rats were trained in a two-phase radial-arm maze procedure, consisting of acquisition and retrieval tests, which were separated by an 18 h delay. Each drug was administered 30 min before the acquisition phase, immediately after the acquisition phase, or 30 min before the retrieval test to assess acquisition/consolidation, consolidation, and retrieval mnemonic processes, respectively. Rimonabant or donepezil administered before the acquisition phase, but not immediately after acquisition or before retrieval, led to a significant decrease in the number of errors committed during the retrieval test. Combined administration of subthreshold doses of rimonabant and donepezil that had no discernable effects on performance when given alone, enhanced memory. These results taken together demonstrate that the delay radial-arm maze task is sufficiently sensitive to detect memory enhancing effects of these drugs. Moreover, these findings suggest that combined administration of subthreshold doses of rimonabant and donepezil can improve memory and may represent a novel approach to treat cognitive deficits associated with neurodegenerative disorders.
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PMID:Combination of rimonabant and donepezil prolongs spatial memory duration. 1721 45

Cannabinoids acting on CB(1) receptors induce learning and memory impairments. However, the identification of novel non-CB(1) receptors which are insensitive to the psychoactive ingredient of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) but sensitive to synthetic cannabinoids such as WIN55,212-2 (WIN-2) or endocannabinoids like anandamide lead us to question whether WIN-2 induced learning and memory deficits are indeed mediated by CB(1) receptor activation. Given the relative paucity of receptor subtype specific antagonists, a way forward would be to determine the transmitter systems, which are modulated by the respective cannabinoids. This study set out to evaluate this proposition by determination of the effects of WIN-2 on acquisition of spatial reference memory using the water maze in rats. Particular weight was given to performance in trial 1 of each daily session as an index of between-session long-term memory, and in trial 4 as an index of within-session short-term memory. Intraperitoneal (i.p.) administration of WIN-2 (1 mg/kg and 3 mg/kg) prior to training impaired long-term, but not short-term memory. This deficit was not reversed by the CB(1) antagonists/inverse agonists Rimonabant (3mg/kg i.p.) and AM281 (0.5 mg/kg i.p.), but recovered in the presence of the cholinesterase inhibitor rivastigmine (1 mg/kg). Reversal by rivastigmine was specific to WIN-2, as it failed to reverse MK801 (0.08 mg/kg) induced learning impairments. Collectively, these data suggest that in this spatial reference memory task WIN-2 causes a reduction in cholinergic activation, possibly through a non-CB(1)-like mechanism, which affects long-term but not short-term spatial memory.
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PMID:WIN55,212-2 induced deficits in spatial learning are mediated by cholinergic hypofunction. 2007 75