Methamphetamine-induced dopamine-independent alterations in striatal gene expression in the 6-hydroxydopamine hemiparkinsonian rats

• Published in: PloS one 2010-12, Vol.5 (12), p.e15643-e15643
• Main Authors: Cadet, Jean Lud, Brannock, Christie, Krasnova, Irina N, Ladenheim, Bruce, McCoy, Michael T, Chou, Jenny, Lehrmann, Elin, Wood, William H, Becker, Kevin G, Wang, Yun
• Format: Article
• Language: English
• Subjects: 6-Hydroxydopamine; Addictive behaviors; Amphetamines; Animals; Behavior; Biology; Brain; Brain cancer; Brain research; c-Fos protein; Chromatography, High Pressure Liquid - methods; Corpus Striatum - metabolism; Cyclooxygenase-2; Depletion; DNA microarrays; DNA-Binding Proteins - biosynthesis; Dopamine; Dopamine - metabolism; Dopamine receptors; Dopamine Uptake Inhibitors - pharmacology; Drug abuse; Early Growth Response Protein 1 - biosynthesis; EGR-1 protein; Follistatin; Forebrain; Fos protein; Gene expression; Gene Expression Regulation; Genes; Genomics; Growth factors; Injection; Laboratory animals; Male; Medial forebrain bundle; Mediation; Medicine; Methamphetamine; Methamphetamine - pharmacology; Movement disorders; Neostriatum; Nerve Tissue Proteins - biosynthesis; Neurodegenerative diseases; Neuromedin; Neurosciences; Neurotoxicity; Oligonucleotide Array Sequence Analysis; Oxidopamine - chemistry; Oxidopamine - metabolism; Parkinson Disease - metabolism; Parkinson's disease; Phenols (Class of compounds); Platelet-derived growth factor; Protein expression; Proteins; Proto-Oncogene Proteins c-fos - biosynthesis; Rats; Rats, Sprague-Dawley; Rodents; Serotonin; Tachykinin; Tachykinin receptors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0015643

Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are used extensively as a model of Parkinson's disease. The present experiments sought to identify genes that were affected in the dopamine (DA)-denervated striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal dopaminergic pathway in the rat. We also examined whether a single injection of methamphetamine (METH) (2.5 mg/kg) known to cause changes in gene expression in the normally DA-innervated striatum could still influence striatal gene expression in the absence of DA. Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle resulted in METH-induced rotational behaviors ipsilateral to the lesioned side and total striatal DA depletion on the lesioned side. This injection also caused decrease in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. DA depletion was associated with increases in 5-HIAA/5-HT ratios that were potentiated by the METH injection. Microarray analyses revealed changes (±1.7-fold, p