Repeated cocaine administration alters the expression of genes in corticolimbic circuitry after a 3‐week withdrawal: a DNA macroarray study

• Published in: Journal of neurochemistry Vol. 82; no. 5; pp. 1290 - 1299
• Main Authors: Toda, Shigenobu, McGinty, Jacqueline F., Kalivas, Peter W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2002; Blackwell
• Subjects: adenosine A1 receptor; Animals; Biological and medical sciences; Caudate Nucleus - drug effects; Caudate Nucleus - metabolism; cDNA array; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chronic Disease; Cocaine - administration & dosage; Cocaine-Related Disorders - metabolism; Disease Models, Animal; Drug addictions; Drug Administration Schedule; Gene Expression Regulation - drug effects; glutamate receptor 5; Immunoblotting; Limbic System - drug effects; Limbic System - metabolism; Male; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; neuroglycan C; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Oligonucleotide Array Sequence Analysis; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Proteoglycans - genetics; Proteoglycans - metabolism; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Receptors, Kainic Acid - genetics; Receptors, Kainic Acid - metabolism; Receptors, Purinergic P1 - genetics; Receptors, Purinergic P1 - metabolism; repeated cocaine; RNA, Messenger - metabolism; Toxicology; TrkB; Rat; neuroglycan C; Toxicity; Central nervous system; DNA chip; Alteration; A1 Adenosine receptor; Glutamate receptor; Encephalon; trkB receptor; cDNA array; Poison withdrawal; Rodentia; Basal ganglion; Prefrontal cortex; Gene expression; adenosine A1 receptor; repeated cocaine; Nucleus accumbens; Vertebrata; TrkB; glutamate receptor 5; Mammalia; Addiction; Complementary DNA; Animal; Cocaine
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2002.01083.x

Addiction to psychostimulants elicits behavioral and biochemical changes that are assumed to be mediated by alterations of gene expression in the brain. The changes in gene expression after 3 weeks of withdrawal from chronic cocaine treatment were evaluated in the nucleus accumbens core and shell, dorsal prefrontal cortex and caudate using a complementary DNA (cDNA) array. The level of mRNA encoded by several genes was identified as being up‐ or down‐regulated in repeated cocaine versus saline subjects. The results from the cDNA array were subsequently confirmed at the protein level with immunoblotting. Of particular interest, parallel up‐regulation in protein and mRNA was found for the adenosine A1 receptor in the accumbens core, neuroglycan C in the accumbens shell, and the GluR5 glutamate receptor subtype in dorsal prefrontal cortex. However, there was an increase in TrkB protein in the nucleus accumbens core of cocaine‐treated rats without a corresponding alteration in mRNA. These changes of gene expression in corticolimbic circuitry may contribute to the psychostimulant‐induced behavioral changes associated with addiction.