Document Detail


WIN55,212-2 induced deficits in spatial learning are mediated by cholinergic hypofunction.
MedLine Citation:
PMID:  20079375     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lianne Robinson; Anushka V Goonawardena; Roger Pertwee; Robert E Hampson; Bettina Platt; Gernot Riedel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-14
Journal Detail:
Title:  Behavioural brain research     Volume:  208     ISSN:  1872-7549     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-05-25     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  584-92     Citation Subset:  IM    
Copyright Information:
Copyright 2010. Published by Elsevier B.V.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / metabolism*
Animals
Benzoxazines* / pharmacology
Cannabinoid Receptor Agonists
Cholinergic Antagonists / pharmacology
Disease Models, Animal
Dizocilpine Maleate / pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Excitatory Amino Acid Antagonists / pharmacology
Learning Disorders / chemically induced*,  metabolism*
Male
Maze Learning / drug effects
Memory / drug effects
Morpholines* / pharmacology
Naphthalenes* / pharmacology
Piperidines / pharmacology
Pyrazoles / pharmacology
Rats
Scopolamine Hydrobromide / pharmacology
Spatial Behavior / drug effects*
Grant Support
ID/Acronym/Agency:
DA08549/DA/NIDA NIH HHS; R01 DA008549/DA/NIDA NIH HHS; R01 DA008549-14A1/DA/NIDA NIH HHS; R01 DA008549-15/DA/NIDA NIH HHS; //Medical Research Council
Chemical
Reg. No./Substance:
0/AM 281; 0/Benzoxazines; 0/Cannabinoid Receptor Agonists; 0/Cholinergic Antagonists; 0/Excitatory Amino Acid Antagonists; 0/Morpholines; 0/Naphthalenes; 0/Piperidines; 0/Pyrazoles; 134959-51-6/Win 55212-2; 158681-13-1/rimonabant; 451IFR0GXB/Scopolamine Hydrobromide; 6LR8C1B66Q/Dizocilpine Maleate; N9YNS0M02X/Acetylcholine
Comments/Corrections

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