Project description:The objective of this study was to determine common innate differences in gene expression in the ventral tegmental area (VTA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. There were between 350 and 1400 unique named genes that were significantly different between the individual line-pairs. Gene Ontology (GO) and Ingenuity Pathways analyses indicated significant categories and networks in common for up to 3 line-pairs, but not for all 5 line-pairs; there were few genes in common between any of the line-pairs in these categories and networks. The overall ANOVAs of the combined data for the 5 line-pairs indicated over 1300 significant differences in expression of named genes. Ingenuity analysis revealed (a) several significant networks with clusters of genes associated with App, Egfr, Ccnd1, Itga2b, Rxra and Vcl; and (b) changes in genes within networks associated with dopamine, the glutamate synapse, Nfkb signaling, IL pathways and integrin. There were 22 genes that were significantly different in the overall ANOVA and were significantly different (in the direction) in at least 3 line-pairs, e.g., Crebl2, Gsta4, Itga9 & Itg2. In conclusion, the findings suggest that (a) different innate mechanisms may be contributing to vulnerability to high alcohol drinking behavior among the selectively bred lines, and (b) small contributions in expression of multiple genes within certain transmitter systems and intracellular signaling pathways may contribute to the disparate alcohol drinking characteristics of the 5 line-pairs. Comparison of Differences in Gene Expression in the Ventral Tegmental Area of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption.
Project description:The objective of this study was to determine changes in gene expression in the ventral tegmental area (VTA) following loss-of-control alcohol drinking by alcohol-preferring (P) rats. Adult female P rats (n = 7) were given concurrent access to 10, 20 and 30% EtOH for four 1-hr sessions daily for 10 weeks followed by 2 cycles of 2 weeks of abstinence and 2 weeks of EtOH access. Rats were killed by decapitation 3 hr after the 4th daily EtOH-access session at the end of the second 2-week relapse period. An age-matched water control group of female P rats (n = 8) was also killed. RNA was prepared from micropunch samples of the VTA from individual rats; analyses were conducted with Affymetrix Rat 230.2 chips. Ethanol intakes were 1.5-2.5 g/kg per sessions, resulting in blood levels >200 mg% at the end of the 4th session. There were 211 named genes that were significantly different (FDR = 0.1) between the water and EtOH groups. Bioinformatics analyses indicated alterations in (a) transcription factors that reduced excitation-coupled transcription and promoted exocitotic neuronal damage involving clusters of genes associated with Nfkbia, Fos and Srebf1; (b) genes that reduced cholesterol and fatty acid synthesis, and increased protein degradation; and (c) genes involved in cell-to-cell interactions and regulation of the actin cytoskeleton. Among the named genes, there were 62 genes in common with differences between alcohol-naïve P and non-preferring (NP) rats, with 43 of the genes changing in the opposite direction following excessive binge-like drinking. These genes are involved in a pro-inflammatory response, and enhanced response to glucocorticoids and steroid hormones. Overall, the results of this study indicated that excessive binge-like alcohol drinking by P rats may be altering the expression of genes that promote neuronal damage. Comparison of Differences in Gene Expression in the Ventral Tegmental Area of Rat Lines Selectively Bred for High or Low Alcohol Consumption
Project description:The objective of this study was to determine common innate differences in gene expression in the ventral tegmental area (VTA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. There were between 350 and 1400 unique named genes that were significantly different between the individual line-pairs. Gene Ontology (GO) and Ingenuity Pathways analyses indicated significant categories and networks in common for up to 3 line-pairs, but not for all 5 line-pairs; there were few genes in common between any of the line-pairs in these categories and networks. The overall ANOVAs of the combined data for the 5 line-pairs indicated over 1300 significant differences in expression of named genes. Ingenuity analysis revealed (a) several significant networks with clusters of genes associated with App, Egfr, Ccnd1, Itga2b, Rxra and Vcl; and (b) changes in genes within networks associated with dopamine, the glutamate synapse, Nfkb signaling, IL pathways and integrin. There were 22 genes that were significantly different in the overall ANOVA and were significantly different (in the direction) in at least 3 line-pairs, e.g., Crebl2, Gsta4, Itga9 & Itg2. In conclusion, the findings suggest that (a) different innate mechanisms may be contributing to vulnerability to high alcohol drinking behavior among the selectively bred lines, and (b) small contributions in expression of multiple genes within certain transmitter systems and intracellular signaling pathways may contribute to the disparate alcohol drinking characteristics of the 5 line-pairs.
Project description:The objective of this study was to determine changes in gene expression in the ventral tegmental area (VTA) following loss-of-control alcohol drinking by alcohol-preferring (P) rats. Adult female P rats (n = 7) were given concurrent access to 10, 20 and 30% EtOH for four 1-hr sessions daily for 10 weeks followed by 2 cycles of 2 weeks of abstinence and 2 weeks of EtOH access. Rats were killed by decapitation 3 hr after the 4th daily EtOH-access session at the end of the second 2-week relapse period. An age-matched water control group of female P rats (n = 8) was also killed. RNA was prepared from micropunch samples of the VTA from individual rats; analyses were conducted with Affymetrix Rat 230.2 chips. Ethanol intakes were 1.5-2.5 g/kg per sessions, resulting in blood levels >200 mg% at the end of the 4th session. There were 211 named genes that were significantly different (FDR = 0.1) between the water and EtOH groups. Bioinformatics analyses indicated alterations in (a) transcription factors that reduced excitation-coupled transcription and promoted exocitotic neuronal damage involving clusters of genes associated with Nfkbia, Fos and Srebf1; (b) genes that reduced cholesterol and fatty acid synthesis, and increased protein degradation; and (c) genes involved in cell-to-cell interactions and regulation of the actin cytoskeleton. Among the named genes, there were 62 genes in common with differences between alcohol-naïve P and non-preferring (NP) rats, with 43 of the genes changing in the opposite direction following excessive binge-like drinking. These genes are involved in a pro-inflammatory response, and enhanced response to glucocorticoids and steroid hormones. Overall, the results of this study indicated that excessive binge-like alcohol drinking by P rats may be altering the expression of genes that promote neuronal damage.
Project description:The objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats.
Project description:The objective of this study was to determine common innate differences in gene expression in the Central Nucleus of the Amygdala (CeA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats.
Project description:Drugs of abuse including nicotine and alcohol elicit their effect by stimulating the mesocorticolimbic dopaminergic system. There is a high incidence of nicotine dependence in alcoholics. To date only limited data is available on the molecular mechanism underlying the action of alcohol and nicotine in the human brain. This study utilised gene expression screening to identify genes sensitive to chronic alcohol abuse within the ventral tegmental area of the human brain. Keywords: gene expression, brain, alcohol abuse, human, ventral tegmental area
Project description:The objective of this study was to determine common innate differences in gene expression in the nucleus accumbens shell among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. Comparison of Differences in Gene Expression in the Nucleus Accumbens Shell of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption.
Project description:The objective of this study was to determine common innate differences in gene expression in the Central Nucleus of the Amygdala (CeA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats: (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. Comparison of Differences in Gene Expression in the Central Nucleus of the Amygdala (CeA) of 5 Pairs of Rat Lines Selectively Bred for High or Low Alcohol Consumption.
Project description:Rats were trained to orally self-administer alcohol in a concurrent, two-lever, free-choice contingency using a modification of the sweet solution fading procedure (O'Dell et al., 2004; Roberts et al., 2000; Vendruscolo et al., 2012). Following acquisition of self-administration, rats were allowed to self-administer unsweetened alcohol (10%) for 4 weeks and were then assigned to two groups matched by levels of responding: one group (dependent group) was exposed to chronic, intermittent ethanol vapors for 4 weeks to induce dependence; the other group (nondependent group) was not exposed to ethanol vapor. After a month of vapor exposure, rats were again tested during acute withdrawal (6-8 hours after removal from the vapor chambers) until stable levels of alcohol intake were achieved. As expected, alcohol vapor-exposed rats self-administered significantly greater amounts of alcohol than control rats not exposed to alcohol vapor during acute withdrawal. Rats were sacrificed during protracted abstinence (3 weeks after the end of alcohol vapor exposure) along with age-matched alcohol naive rats. 96 gene expression profiles (GEP) were obtained from 8 brain regions believed to be relevant in alcoholM-bM-^@M-^Ys reinforcing properties using the Affymetrix RN230.2 platform. Specifically, the following brain regions were microdissected and analyzed from nondependent and dependent alcohol self-administering rats as well as age-matched alcohol naive rats: (a) medial prefrontal cortex (MPF), (b) shell and (c) core NAc sub-regions, (d) central nucleus (CeA) and (e) basolateral nucleus of the amygdala (BLA), (f) dorsolateral and (g) ventral bed nucleus of the stria terminalis (BNST), and (h) ventral tegmental area (VTA).