Role of Corticotropin-Releasing Factor and Corticosterone in Behavioral Sensitization to Ethanol
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Other documents of the author: Pastor Medall, Raúl; Reed, Cheryl; Meyer, Paul J.; McKinnon, Carrie; Ryabinin, Andrey E.; Phillips, Tamara J.
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comunitat-uji-handle2:10234/8033
comunitat-uji-handle3:10234/8636
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http://dx.doi.org/10.1124/jpet.111.190595 |
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Title
Role of Corticotropin-Releasing Factor and Corticosterone in Behavioral Sensitization to EthanolAuthor (s)
Date
2012Publisher
American Society for Pharmacology and Experimental TherapeuticsISSN
0022-3565Type
info:eu-repo/semantics/articlePublisher version
http://jpet.aspetjournals.org/content/early/2012/02/14/jpet.111.190595Version
info:eu-repo/semantics/publishedVersionAbstract
Neuroadaptations underlying sensitization to drugs of abuse seem to influence compulsive drug pursuit and relapse associated with addiction. Our previous data support a role for the corticotropin-releasing factor (CRF) ... [+]
Neuroadaptations underlying sensitization to drugs of abuse seem to influence compulsive drug pursuit and relapse associated with addiction. Our previous data support a role for the corticotropin-releasing factor (CRF) type-1 receptor (CRF1) in ethanol (EtOH)-induced psychomotor sensitization. CRF1 is endogenously activated by CRF and urocortin-1. Because genetic deletion of urocortin-1 did not affect EtOH sensitization, we hypothesized that CRF is the important ligand underlying EtOH sensitization. To test this hypothesis, we used heterozygous and homozygous knockout (KO) mice, which lack one or both copies of the gene coding for CRF, and their respective wild-type controls. EtOH sensitization was normal in heterozygous, but absent in homozygous, CRF KO mice. Corticosterone (CORT) levels were drastically reduced only in CRF KO mice. Because CRF/CRF1 initiate EtOH-induced activation of the hypothalamic-pituitary-adrenal axis, we investigated CORT effects on EtOH sensitization. The CORT synthesis inhibitor metyrapone prevented the acquisition, but not the expression, of EtOH sensitization. Exogenous CORT administration sensitized the locomotor response to a subsequent EtOH challenge; we observed, however, that the exogenous CORT levels necessary to induce sensitization to EtOH were significantly higher than those produced by EtOH treatment. Therefore, participation of CORT seems to be necessary, but not sufficient, to explain the role of CRF/CRF1 in the acquisition of sensitization to EtOH. Extra-hypothalamic CRF/CRF1 mechanisms are suggested to be involved in the expression of EtOH sensitization. The present results are consistent with current theories proposing a key role for CRF and CRF1 in drug-induced neuroplasticity, dependence, and addictive behavior. [-]
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The Journal of Pharmacology and Experimental Therapeutics , 341, 2Rights
Copyright 2012 The American Society for Pharmacology and Experimental Therapeutics
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