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The Journal of Neuroscience, September 20, 2006, 26(38):9656-9665; doi:10.1523/JNEUROSCI.2391-06.2006

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Behavioral/Systems/Cognitive
Altered Attention and Prefrontal Cortex Gene Expression in Rats after Binge-Like Exposure to Cocaine during Adolescence

Yolanda D. Black,^1,3 Fair R. Maclaren,¹ Alipi V. Naydenov,¹ William A. Carlezon, Jr,^2,3 Mark G. Baxter,⁴ and Christine Konradi^1,3

¹Laboratory of Neuroplasticity and ²Behavioral Genetics Laboratory, McLean Hospital, Belmont, Massachusetts 02478, ³Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115, and ⁴Department of Experimental Psychology, Oxford University, Oxford OX1 3UD, United Kingdom

Correspondence should be addressed to Christine Konradi, Vanderbilt University, MRB 3, BioSciences Building, Room 7158C, 465 21st Avenue South, Nashville, TN 37232. Email: christine.konradi{at}vanderbilt.edu

Illicit use of drugs frequently begins and escalates during adolescence, with long-term adverse consequences. Because it is increasingly accepted that neural development continues through adolescence, addiction research has become more invested in understanding the behavioral and molecular consequences of early exposure to drugs of abuse. In a novel binge administration paradigm designed to model the pattern of human adolescent drug use, we administered ascending doses of cocaine or saline during a 12-d developmental period [postnatal day 35 (P35) to P46] corresponding to human adolescence. During adulthood (P70), rats treated with this regimen displayed increased responsiveness to the stimulant effects of cocaine. Adult rats also displayed abnormally rapid shifts in attention when performing an attentional set-shifting task, which measures the ability to shift attention between stimuli and whose performance requires an intact prefrontal cortex (PFC). Treatment with cocaine during adolescence also caused acute alterations in the expression of genes encoding cell adhesion molecules and transcription factors within the PFC. Furthermore, we observed decreases in histone methylation, which may indicate a role for chromatin remodeling in the observed changes in gene expression patterns. These findings suggest that exposure to cocaine during adolescence has far-reaching molecular and behavioral consequences in the rat PFC that develop over time and endure long after drug administration has ceased.

Key words: medial prefrontal cortex; attentional set-shifting task; cell adhesion; adolescence; cocaine; gene expression

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Received March 30, 2006; revised July 21, 2006; accepted Aug. 10, 2006.

Correspondence should be addressed to Christine Konradi, Vanderbilt University, MRB 3, BioSciences Building, Room 7158C, 465 21st Avenue South, Nashville, TN 37232. Email: christine.konradi{at}vanderbilt.edu

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				G. B. Bissonette, G. J. Martins, T. M. Franz, E. S. Harper, G. Schoenbaum, and E. M. Powell Double Dissociation of the Effects of Medial and Orbital Prefrontal Cortical Lesions on Attentional and Affective Shifts in Mice J. Neurosci., October 29, 2008; 28(44): 11124 - 11130. [Abstract] [Full Text] [PDF]

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