Mouse striatal transcriptome analysis: effects of oral self-administration of alcohol

It is believed that drug-induced behavioral sensitization is an important process in the development of substance dependence. In order to explore mechanisms of sensitization, a mouse model of nicotine-induced locomotor sensitization was established, and effects of the sensitization process on mesencepahlic gene expression were examined. A schedule, which included 3 weeks of intermittent nicotine exposure (0.5 mg/kg, s.c.) and 3 weeks of withdrawal, resulted in locomotor sensitization. Effects of sensitization on mesencephalic expression of approximately 14,000 genes were assessed using oligonucleotide microarrays. Signal intensity differences in samples obtained from repeated nicotine- and saline-exposed animals were analyzed with z-test after False Discovery Rate (FDR) multiple test correction. Genes related to GABA-A receptors and protein phosphatases were among 68 genes showing significantly different expression levels between the saline and the nicotine groups. We hypothesize that some of the gene expression changes in the mesencephalon are involved in pathways leading to nicotine-induced sensitization. Down-regulation of GABA-A receptors induced by repeated nicotine exposure may facilitate dopaminergic neuronal transmission and may contribute to increased locomotor activity.

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“…A similar strategy was applied in a recent study on the effects of alcohol drinking on the striatal transcriptome (24).…”

Section: Methodsmentioning

confidence: 93%

“…Quantitative real time PCR (qPCR) experiments were performed as described previously (24). RNA isolated from the mesencephalon of each animal was reverse-transcribed, and qPCR was performed with a SYBR Green method using an ABI Prism 7900 sequence-detection system (Applied Biosystems, Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

Nicotine-Induced Sensitization in Mice: Changes in Locomotor Activity and Mesencephalic Gene Expression

et al. 2005

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“…Thus, it is not unreasonable to propose that an ethanol-induced decrease in transthyretin expression in the mutants may be associated with increased ethanol toxicity and decreased viability of the mutants during chronic ethanol treatment. Microarray studies have been performed to elucidate genes that regulate acute responses to ethanol (Kerns et al 2005;Kwon et al 2004) that underlie genetic differences in inbred and selected lines of rodents (Edenberg et al 2004;Saito et al 2004, Spence et al 2005Thibault et al 2000), the effects of chronic ethanol treatment or withdrawal in rodents and worms (Daniels and Buck 2002;Kwon et al 2004;Rimondini et al 2002Saito et al 2002, and the effects of long-term alcohol use in humans (Flatscher-Bader et al 2005;Lewohl et al 2000;Mayfield et al 2002). These studies varied in experimental design (for review see Rahman and Miles 2001;Worst and Vrana 2005).…”

Section: Transthyretin and Chronic Ethanol Treatmentmentioning

confidence: 98%

Microarray Analysis of the Effects of a γ-protein Kinase C Null Mutation on Gene Expression in Striatum: A Role for Transthyretin in Mutant Phenotypes

Smith

Bowers²,

Radcliffe

et al. 2006

Behav Genet

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A constitutive null mutation of the neural-specific isotype of protein kinase C (gamma-PKC) in mice produces alterations in behavioral traits and responses to ethanol suggesting that gamma-PKC-mediated phosphorylation is essential for regulation of some behaviors. However, it is possible that some of the effects of gamma-PKC gene deletion also may be due to altered gene expression. To examine alterations in gene expression, microarray analyses were performed on striatal tissue from wild types and mutants. A total of 143 genes and ESTs were identified as potential candidates related to differences between null mutants and wild types. Confirmation studies using qRT-PCR indicated that the expression of transthyretin was increased about 8-fold in striatum of naïve mutants compared to wild types. The effect of chronic ethanol treatment on transthyretin expression was analyzed because gamma-PKC mutants do not develop tolerance to chronic ethanol treatment. Ethanol treatment of mutants reversed the dramatic increase in transthyretin expression seen in naïve and control-diet treated mutants, but did not affect transthyretin expression in wild types.

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“…The yield For quantitative real-time polymerase chain reaction (qPCR) experiments, 6 mice in the control group and 3 in the nicotine treatment group from each strain (B6By, BALB/cJ, C4A4, I5B25A) were used. RNA isolated from the ventral tegmentum as described above was treated with amplification-grade deoxyribonuclease I (Invitrogen) and reverse-transcribed using a SuperScript First-Strand Synthesis System for RT-PCR (Invitrogen) with oligo(dT) primers as described previously [51]. qPCR was performed with a SYBR Green method using an ABI Prism 7900 sequencedetection system (Applied Biosystems, Foster City, CA).…”

Section: Drugsmentioning

confidence: 99%

Ventral Tegmental Transcriptome Response to Intermittent Nicotine Treatment and Withdrawal in BALB/cJ, C57BL/6ByJ, and Quasi-Congenic RQI Mice

et al. 2007

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The aim of this study was to identify neurochemical pathways and candidate genes involved in adaptation to nicotine treatment and withdrawal. Locomotor sensitization was assessed in a nicotine challenge test after exposure to intermittent nicotine treatment and withdrawal. About 24 h after the challenge test the ventral tegmentum of the mesencephaion was dissected and processed using oligonucleotide microarrays with 22,690 probe sets (Affymetrix 430A 2.0). Quasi-congenic RQI, and donor BALB/cJ mice developed significant locomotor sensitization, while sensitization was not significant in the background partner, C57BL/6By. Comparing saline treated controls of C57BL/6ByJ and BALB/cJ by a rigorous statistical microarray analysis method we identified 238 differentially expressed transcripts. Quasi-congenic strains B6.Cb4i5-alpha4/Vad and B6.Ib5i7-beta25A/Vad significantly differed from the background strain in 11 and 11 transcripts, respectively. Identification of several cis- and trans-regulated genes indicates that further work with quasi-congenic strains can quickly lead to mapping of Quantitative Trait Loci for nicotine susceptibility because donor chromosome regions have been mapped in quasi-congenic strains. Nicotine treatment significantly altered the abundance of 41, 29, 54, and 14 ventral tegmental transcripts in strains C57BL/6ByJ, BALB/cJ, B6.Cb4i5-alpha4/Vad, and B6.Ib5i7-beta25A/Vad, respectively. Although transcript sets overlapped to some extent, each strain showed a distinct profile of nicotine sensitive genes, indicating genetic effects on nicotine-induced gene expression. Nicotine-responsive genes were related to processes including regulation of signal transduction, intracellular protein transport, proteasomal ubiquitin-dependent protein catabolism, and neuropeptide signaling pathway. Our results suggest that while there are common regulatory mechanisms across inbred strains, even relatively small differences in genetic constitution can significantly affect transcriptome response to nicotine.

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Mouse striatal transcriptome analysis: effects of oral self-administration of alcohol

Cited by 29 publications

References 51 publications

Nicotine-Induced Sensitization in Mice: Changes in Locomotor Activity and Mesencephalic Gene Expression

Nicotine-Induced Sensitization in Mice: Changes in Locomotor Activity and Mesencephalic Gene Expression

Microarray Analysis of the Effects of a γ-protein Kinase C Null Mutation on Gene Expression in Striatum: A Role for Transthyretin in Mutant Phenotypes

Ventral Tegmental Transcriptome Response to Intermittent Nicotine Treatment and Withdrawal in BALB/cJ, C57BL/6ByJ, and Quasi-Congenic RQI Mice

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