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The influence of adolescent nicotine exposure on ethanol intake and brain gene expression.

ABSTRACT: Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. It is possible that during this vulnerable period, use of one drug leads to neurobiological alterations that affect subsequent consumption of the other drug. The aim of the present study was to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of these substances on brain gene expression. Forty-three adolescent female C57BL/6J mice were assigned to four groups. In the first phase of the experiment, adolescent mice (PND 36-41 days) were exposed to three bottles filled with water or nicotine (200 ?g/ml) for 22 h a day and a single bottle of water 2 h a day for six days. In the second phase (PND 42-45 days), the 4-day Drinking-in-the-Dark paradigm consisting of access to 20% v/v ethanol or water for 2h or 4h (the last day) was overlaid during the time when the mice did not have nicotine available. Ethanol consumption (g/kg) and blood ethanol concentrations (BEC, mg %) were measured on the final day and whole brains including the cerebellum, were dissected for RNA sequencing. Differentially expressed genes (DEG) were detected with CuffDiff and gene networks were built using WGCNA. Prior nicotine exposure increased ethanol consumption and resulting BEC. Significant DEG and biological pathways found in the group exposed to both nicotine and ethanol included genes important in stress-related neuropeptide signaling, hypothalamic-pituitary-adrenal (HPA) axis activity, glutamate release, GABA signaling, and dopamine release. These results replicate our earlier findings that nicotine exposure during adolescence increases ethanol consumption and extends this work by examining gene expression differences which could mediate these behavioral effects.

SUBMITTER: Silva CP

PROVIDER: S-EPMC6005571 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The influence of adolescent nicotine exposure on ethanol intake and brain gene expression.

Silva Constanza P CP Horton William J WJ Caruso Michael J MJ Sebastian Aswathy A Klein Laura C LC Albert Istvan I Kamens Helen M HM

PloS one 20180618 6

Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. It is possible that during this vulnerable period, use of one drug leads to neurobiological alterations that affect subsequent consumption of the other drug. The aim of the present study was to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of th ...[more]

PMID: 29912970

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Project description:Background: Nicotine and alcohol are often co-abused. Adolescence is a vulnerable period for the initiation of both nicotine and alcohol use, which can lead to subsequent neurodevelopmental and behavioral alterations. Aim: The aim was to to determine the effect of nicotine exposure during adolescence on ethanol intake, and the effect of both substances on brain gene expression. Methods: RNA was extracted from a randomly selected subset of mice (16 total; 4 samples from each experimental group). Whole brains (including cerebellum) were dissected. Total RNA was extracted with an RNeasy® Midi Kit (QIAGEN, Valencia, CA). RNA quality was assessed using an Agilent 2100 BioAnalyzer™. An Illumina TruSeq® Stranded mRNA Library Prep Kit (Illumina, San Diego, CA) was used for cDNA library preparation following the manufacturers’ protocol. Libraries were sequenced using an Illumina HiSeq 2500 (Illumina, San Diego, CA). Trimmomatic was used to remove sequencing adapters and low-quality ends. The cleaned dataset was analyzed with the Tuxedo pipeline. Subsequently, readings were mapped to the mouse reference genome (Ensembl GRCm38, mm10) using TopHat2 software (http://tophat.cbcb.umd.edu/). The ‘--library_type’ parameter was set to ‘fr-firststrand’. Default settings were preserved for all other TopHat2 parameters. The resulting alignments files from TopHat2 were used to generate a transcriptome assembly. Gene expression was calculated for each condition using the Cufflinks and Cuffmerge utilities. Cuffdiff2 with default settings was used to identify transcripts that were differentially expressed between each treatment group compared to the water only control group.The significance threshold was set at q < 0.05 (FDR corrected). Finally, a Fisher’s exact test was performed using the GeneOverlap R package to test the significance of DEG overlaps. Gene co-expression networks were identified using the Weighted Gene Co-expression Network Analysis (WGCNA) package. Results: RNA Integrity Number (RIN) was on average 8.23 ± 0.26 for all samples, suggesting high RNA integrity and quality. On average, 43 million, 150 base pair single end reads were generated for each sample and used in the analysis. The resulting alignments files from TopHat2 had an average mapping rate of 87.4%.

Dataset Information

The influence of adolescent nicotine exposure on ethanol intake and brain gene expression.

Publications

The influence of adolescent nicotine exposure on ethanol intake and brain gene expression.

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