Cocaine interacts with the novelty-seeking trait to modulate FGFR1 gene expression in the rat.
The present study sought to determine the interaction between the novelty-seeking trait and cocaine treatment on gene expression in the fibroblast growth factor (FGF) system. Specifically, we assessed the regulation of FGFR1 in response to cocaine in animals that were selectively bred on the basis of their locomotor response to a novel environment. High-responder (HR) rats are those that exhibit increased locomotor response and exploratory behavior in a novel environment and low-responder (LR) rats are those that exhibit lower levels of exploratory behavior and are less active. Both phenotypes received daily injections of either cocaine (15 mg/kg, i.p.) or saline for 7 consecutive days. Animals were sacrificed 45 min following their last injection and FGFR1 gene expression was assessed in the hippocampus and prefrontal cortex by mRNA in situ hybridization. HR-bred rats exhibited increased FGFR1 mRNA in the hippocampus compared to LR-bred rats. Furthermore, cocaine decreased FGFR1 mRNA in the hippocampus and increased FGFR1 mRNA in the prefrontal cortex. Finally, HR and LR rats differed in their response to cocaine between brain regions. In the hippocampus, cocaine decreased gene expression in HR-bred rats without affecting LR-bred rats, whereas in the prefrontal cortex cocaine increased gene expression in LR-bred rats without affecting HR-bred rats. These results suggest that cocaine interacts with the novelty-seeking trait to alter gene expression. Thus, the FGF system may contribute to individual differences in the response to drugs of abuse.
Turner
Cortney A
CA
Molecular and Behavioral Neuroscience Institute, 205 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, USA. caturner@umich.edu
Flagel
Shelly B
SB
Clinton
Sarah M
SM
Akil
Huda
H
Watson
Stanley J
SJ
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004777:Environment; D004780:Environment, Controlled; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1; D003042:Cocaine