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- W2102067349 abstract "Repeated exposure to cocaine results in neuroadaptations that can alter the way the brain responds to subsequent stimuli. Earlier studies demonstrated that acute administration of cocaine up-regulates the immediate-early gene fos-related antigen 2 (fra-2) followed by a later up-regulation of σ<sub>1</sub> receptor gene and protein levels in brain regions involved in addiction and reward. To test whether such alterations could have long-term consequences on behavior, the present study was undertaken. Using a cocaine-induced behavioral sensitization model coupled with gene and protein expression studies in mice, the results show that cocaine induces the expression of fra-2, which leads to a progressive increase in σ<sub>1</sub> receptor gene and protein expression over a period of days. This progressive increase in σ<sub>1</sub> expression corresponds to the steady increase in the locomotor response to repeated cocaine administration in mice. The cocaine-induced changes in fra-2 and σ<sub>1</sub> receptor gene and protein expression occur in brain regions that subserve drug abuse, such as the cortex, striatum, and hippocampus, but not the cerebellum. Moreover, the prototypic σ<sub>1</sub> receptor antagonist 1-[2-(3,4-dichloropheny)ethyl]-4-methylpiperazine (BD1063) significantly attenuates both the molecular adaptations and behavioral sensitization induced by cocaine. These data suggest that repeated exposure to cocaine elicits alterations in fra-2 and σ<sub>1</sub> receptor-mediated mechanisms, which ultimately manifest as altered behavioral responses to cocaine." @default.
- W2102067349 created "2016-06-24" @default.
- W2102067349 creator A5003065832 @default.
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- W2102067349 date "2008-06-30" @default.
- W2102067349 modified "2023-09-23" @default.
- W2102067349 title "Alterations in Fos-Related Antigen 2 and σ<sub>1</sub> Receptor Gene and Protein Expression Are Associated with the Development of Cocaine-Induced Behavioral Sensitization: Time Course and Regional Distribution Studies" @default.
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- W2102067349 doi "https://doi.org/10.1124/jpet.108.141051" @default.
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