PT  - JOURNAL ARTICLE
AU  - Yun Liu
AU  - Guang-Di Chen
AU  - Megan R. Lerner
AU  - Daniel J. Brackett
AU  - Rae R. Matsumoto
TI  - Cocaine Up-Regulates Fra-2 and σ-1 Receptor Gene and Protein Expression in Brain Regions Involved in Addiction and Reward
AID  - 10.1124/jpet.105.084525
DP  - 2005 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 770--779
VI  - 314
IP  - 2
4099  - http://jpet.aspetjournals.org/content/314/2/770.short
4100  - http://jpet.aspetjournals.org/content/314/2/770.full
SO  - J Pharmacol Exp Ther2005 Aug 01; 314
AB  - σ Receptors have recently been implicated in the actions of cocaine, and antagonists of these receptors prevent many acute and subchronic cocaine effects. A previous study revealed that the immediate early gene fra-2 is up-regulated after cocaine administration, and this effect is prevented by the σ-1 receptor antagonist BD1063 [1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine]. In the present study, the effects of cocaine and BD1063 on the expression of six fos and jun genes were evaluated in mouse brains using cDNA microarrays. Several of these genes were altered by cocaine, but only the alteration in fra-2 was prevented by BD1063. The time courses of fra-2 and σ-1 receptor gene and protein expression in different brain regions were also determined. Cocaine up-regulated fra-2, which was followed by a later up-regulation of σ-1 receptors. The cocaine-induced up-regulation of fra-2 and σ-1 receptor genes and proteins were detected in whole brain, striatum, and cortex, but not in cerebellum. All of these cocaine-induced effects were prevented by BD1063. The interaction between cocaine, fra-2, and σ-1 receptors involves brain regions that are established components of the neural circuit for reward, suggesting that they may contribute to the enduring changes that underlie the cellular basis of drug abuse. The American Society for Pharmacology and Experimental Therapeutics