Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence.
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.
Black
Yolanda D
YD
Laboratory of Neuroplasticity, McLean Hospital, Belmont, Massachusetts 02478, USA.
Maclaren
Fair R
FR
Naydenov
Alipi V
AV
Carlezon
William A
WA
Baxter
Mark G
MG
Konradi
Christine
C
D000367:Age Factors; D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D016739:Behavior, Addictive / Q000378:metabolism / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D003042:Cocaine