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Publication : The glucocorticoid receptor as a potential target to reduce cocaine abuse.

First Author  Deroche-Gamonet V Year  2003
Journal  J Neurosci Volume  23
Issue  11 Pages  4785-90
PubMed ID  12805318 Mgi Jnum  J:132536
Mgi Id  MGI:3776212 Doi  10.1523/JNEUROSCI.23-11-04785.2003
Citation  Deroche-Gamonet V, et al. (2003) The glucocorticoid receptor as a potential target to reduce cocaine abuse. J Neurosci 23(11):4785-90
abstractText  Several findings suggest that glucocorticoid hormones are involved in determining the propensity of an individual to develop cocaine abuse. These hormones activate two related transcription factors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor. In this study, we show that the selective inactivation of the GR gene in the brains of mice profoundly flattened the dose-response function for cocaine intravenous self-administration and suppressed sensitization, two experimental procedures considered relevant models of addiction. Furthermore, administration of a GR antagonist dose-dependently reduced the motivation to self-administer cocaine. Importantly, the absence of GR did not modify the basal behavioral and molecular effects of cocaine but selectively modified the excessive response to the drug spontaneously present in certain vulnerable individuals or induced by repeated drug exposure in others. In conclusion, we provide the first genetic evidence that the GR gene can modulate cocaine abuse. This suggests that targeting GR function in the brain could provide new therapeutic strategies to treat cocaine addiction for which there is no available treatment.
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