Linked Life Data

16914679

Source:http://linkedlifedata.com/resource/pubmed/id/16914679

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2006-8-17
pubmed:abstractText
Blockade of cannabinoid CB1 receptors has been reported to inhibit cocaine- or cocaine cue-induced reinstatement of drug seeking. However, the mechanisms underlying this action are poorly understood. Given the importance of dopamine, glutamate, and GABA in cocaine reward and relapse, we studied the effects of AM251 [N-(piperidin-1-yl)-5-(4-iodophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a novel highly selective CB1 receptor antagonist, on cocaine-primed reinstatement of drug-seeking behavior and on cocaine-induced changes in extracellular DA, glutamate, and GABA in the nucleus accumbens (NAc) under reinstatement conditions. We found that systemic administration of AM251 selectively inhibited cocaine-induced, but not sucrose plus sucrose cue-induced, reinstatement of reward-seeking behavior. AM251 alone did not trigger reinstatement. Local perfusion of AM251 into the NAc or the dorsal striatum also inhibited cocaine-triggered reinstatement. AM251 alone dose dependently elevated NAc glutamate in a voltage-dependent Na+ channel-dependent manner. AM251 did not affect NAc DA or GABA. Pretreatment with AM251 dose dependently inhibited cocaine-induced increases in NAc glutamate but not in DA. Blockade of NAc metabotropic glutamate mGluR2/3 receptors by LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] slightly facilitated cocaine-enhanced glutamate release but blocked the antagonism of cocaine-induced reinstatement by AM251. These data suggest the following: (1) CB1 receptors exert tonic inhibition over NAc glutamate release under cocaine-extinction conditions; (2) blockade of CB1 receptors by AM251 inhibits cocaine-enhanced NAc glutamate release and cocaine-triggered reinstatement; and (3) these effects appear to be mediated by activation of presynaptic mGluR2/3 autoreceptors secondary to AM251-induced increase (disinhibition) of NAc glutamate release.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8531-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Cannabinoid CB1 receptor antagonist AM251 inhibits cocaine-primed relapse in rats: role of glutamate in the nucleus accumbens.
pubmed:affiliation
Neuropsychopharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. zxi@intra.nida.nih.gov
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural