Linked Life Data

10762335

Source:http://linkedlifedata.com/resource/pubmed/id/10762335

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-5-22
pubmed:abstractText
Region-specific up-regulation of the cyclic AMP pathway is considered an important molecular mechanism in the origin of the somatic manifestations of the withdrawal syndrome to known drugs of abuse. Nevertheless, the existence of a withdrawal syndrome after prolonged cannabinoid administration has long been a controversial issue. Recent studies, in different species, have shown that withdrawal to prolonged cannabinoid exposure precipitated by the cannabinoid antagonist SR141716A is characterized by physical signs underlying impairment of motor coordination. Interestingly, cannabinoid withdrawal is accompanied by an increase of adenylyl cyclase activity in the cerebellum. Here, we investigate the functional role of the cyclic AMP pathway in the cerebellum in the establishment of cannabinoid withdrawal. We show that after SR141716A precipitation of cannabinoid withdrawal, basal and calcium-calmodulin-stimulated adenylyl cyclase activities as well as active PKA in the cerebellum increase in a transient manner with a temporal profile which matches that of the somatic expression of abstinence. Selectively blocking the up-regulation of the cyclic AMP pathway in the cerebellum, by microinfusing the cyclic AMP blocker Rp-8Br-cAMPS in this region, markedly reduced both PKA activation and the somatic expression of cannabinoid withdrawal. Our results (i) directly link the behavioural manifestations of cannabinoid withdrawal with the up-regulation of the cyclic AMP pathway in the cerebellum, pointing towards common molecular adaptive mechanisms for dependence and withdrawal to most drugs of abuse; (ii) suggest a particular role for the cerebellum as a major neurobiological substrate for cannabinoid withdrawal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1038-46
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10762335-8-Bromo Cyclic Adenosine Monophosphate, pubmed-meshheading:10762335-Adenylate Cyclase, pubmed-meshheading:10762335-Animals, pubmed-meshheading:10762335-Behavior, Animal, pubmed-meshheading:10762335-Cerebellum, pubmed-meshheading:10762335-Cyclic AMP, pubmed-meshheading:10762335-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10762335-Enzyme Activation, pubmed-meshheading:10762335-Hallucinogens, pubmed-meshheading:10762335-Injections, pubmed-meshheading:10762335-Injections, Intraventricular, pubmed-meshheading:10762335-Male, pubmed-meshheading:10762335-Mice, pubmed-meshheading:10762335-Piperidines, pubmed-meshheading:10762335-Pyrazoles, pubmed-meshheading:10762335-Receptors, Drug, pubmed-meshheading:10762335-Stereotaxic Techniques, pubmed-meshheading:10762335-Substance Withdrawal Syndrome, pubmed-meshheading:10762335-Tetrahydrocannabinol, pubmed-meshheading:10762335-Up-Regulation
pubmed:year
2000
pubmed:articleTitle
Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum.
pubmed:affiliation
INSERM U-99, Unité de Régulations des gènes et signalisation cellulaire, Hôpital. H. Mondor, 94010, Créteil, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't