IUPUI SFN Abstracts 2005

SFN 2005 Abstracts

INDIANA UNIVERSITY - PURDUE UNIVERSITY, INDIANAPOLIS

MODERATE DOSE ACUTE ETHANOL INJECTION ALTERS C-FOS IMMUNOREACTIVITY IN SELECT LIMBIC BRAIN REGIONS OF ALCOHOL-PREFERRING (P) RATS

W.N. Strother; C. Driscoll; L. Lumeng; W.J. McBride

Depts Psych, Med, Indiana Univ Sch Med, Indianapolis, IN, 46202

The immediate early gene c-fos is induced rapidly and transiently by a wide variety of acute stumuli, including drugs of abuse. Mapping c-Fos induction patterns after ethanol (EtOH) administration allows for the identification of brain regions involved in the regulation of alcohol-related behaviors. This method is made more powerful by the utilization of a genetic animal model of alcoholism, the P rat. Adult P rats received an i.p. injection of either saline (n=8) or 1.0 g/kg EtOH (10% v/v) (n=8) and were transcardially perfused 2 hr later with 4% paraformaldehyde and post-fixed overnight. Coronal 40 ƒÊm sections were collected in phosphate buffer using a freezing microtome. Specific c-Fos-ir (Santa Cruz @ 1:10K) was detected using a modified avidin-biotin-immunoperoxidaseprotocol with diaminobenzidine as the chromogen. Sections were slide-mounted and cover-slipped, using standard procedures. Slides were coded and c-Fos-ir was counted in select limbic regions by2 observers blind to treatment group. Acute EtOH injection resulted in significant increases in c-Fos-ir in the bed nucleus of the stria terminalis (BNST), the central nucleus of the amygdala (CeA), and in the medial prefrontal cortex (MPFC) compared to saline injection. In the caudate putamen, EtOH significantly decreased c-Fos-ir. There were no significant differences in c-Fos-ir in subdivisions of the nucleus accumbens, basolateral nucleus of the amygdala, ventral tegmental area (VTA), or lateral septum between treatment groups. The BNST, CeA and MPFC have been suggested to be involved in withdrawal-induced alcohol drinking, and the responsiveness of these regions to the moderate dose of ethanol supports the involvement of these regions in mediating the actions of alcohol. On the other hand, the lack of response of the VTA and nucleus accumbens to the 1.0 g/kg dose was unexpected and could indicate that, although neuronal activity may change in these two regions in response to ethanol, these changes are not reflected in alterations of c-Fos-ir. (AA07611, AA13521 [INIA])

CHRONIC AND BINGE ALCOHOL DRINKING PRODUCE DIFFERENT EFFECTS ON GENE EXPRESSION IN THE NUCLEUS ACCUMBENS OF INBRED ALCOHOL-PREFERRING (IP) RATS

R. L. Bell; Z. A. Rodd; M. Kimple; W. N. Strother; H. Aloor; J.N. McClintick; R. Jerome; W.-M. Liu; L. Lumeng; H. J. Edenberg; W.J. McBride

Depts. Psychiat, Biochem & Med, Indiana University School of Medicine, Indianapolis, IN

The objective of the current study was to examine the effects of oral ethanol (E) consumption on gene expression in the nucleus accumbens (Acb) of iP rats. Male iP rats had binge-like access to E [(B): four 1-hr sessions across dark cycle, 5 days/wk], continuous access to E (C), or served as naïve controls (N). After 7 wks of exposure and 24-hr following the last E access period, animals were euthanized and the Acb dissected. RNA was extracted and purified for microarray analysis.Affymetrix Rat Genome 230 2.0 Array GeneChips were used to analyze differences in gene expression between the groups (n = 6). An Omnibus ANOVA revealed a total of 680 significant differences in gene expression at the p< 0.05 level, and 119 at the p < 0.01 level. Fisher's LSD t-tests were applied to detect expression differences between the groups, which revealed 649 (p < 0.05) or 109 (p < 0.01) differences in expression between N and B groups, 586 (p < 0.05) or 81 (p < 0.01) differences in expression between N and C groups, and 748 (p < 0.05) or 111 (p < 0.01) differences in gene expression between C and B groups. Significantly different levels of gene expression associated with receptors, or receptor-like proteins, were found for the GABA transporter, M3 muscarinic receptor, MGlu-R1 receptor, IGlu-R4 receptor, kappa 1-opioid receptor, CRF binding protein, potassium channel-TREK-2, calcitonin-like receptor, and the G-protein alpha q subunit. Overall, these findings indicate that chronic E drinking alters gene expression for a number of neurotransmitter-neuromodulator associated proteins, and that E drinking conditions influences these alterations. [AA07611, (AA13496, AA13521, AA13522 INIA Projects), INGEN(R)]

ETHANOL SELF-ADMINISTRATION ALTERS GENE EXPRESSION IN THE AMYGDALA OF INBRED ALCOHOL-PREFERRING (IP) RATS

Z. A. Rodd; R. L. Bell; M. Kimple; W. N. Strother; H. Aloor; J.N. McClintick; R. Jerome; W.-M. Liu; L. Lumeng; H. J. Edenberg; W.J. McBride

Depts. Psychiat & Biochem, Indiana University School of Medicine, Indianapolis, IN

The objective of the current study was to examine the effects of operant oral ethanol (E) self-administration on gene expression in the amygdala (Ag) of iP rats. E-naïve iP rats were self-trained on a standard two-lever operant paradigm using daily 1 hr sessions. Rats (n = 6/group) were allowed to self-administer either water-water, E (15% v/v)- water, or saccharin (S; 0.0125%)- water. A concurrent FR5-FR1 schedule of reinforcement was used; the operant task was conducted over a 10-week period. Animals were killed 24 hr after the last operant session and the Ag was dissected; RNA was extracted and purified for microarray analysis. Affymetrix Rat Genome 230 2.0 Array GeneChips were used to analyze differences in gene expression between the animals that self-administered E-water, S-water, and water-water. Comparing across the 3 groups (with ANOVAs), there were 857 significant differences in gene expression at the p< 0.05 level, and 146 at the p < 0.01 level. Additional t-tests were applied to detect expression differences between the groups. There were 1058 (p < 0.05) or 145 (p < 0.01) differences in expression between rats that were allowed to self-administer E-water compared to the water-water group. Comparing E-water and S-water groups, there were 895 (p < 0.05) or 173 (p < 0.01) significant differences in gene expression. Comparing S-water and water-water groups, there were 600 (p < 0.05) or 101 (p < 0.01) significant differences in gene expression. Overall, the data indicated that E self-administration altered the expression of many more genes than did S self-administration. Some genes that were differentially expressed between the E-water group and the other two groups included the NMDA receptor, metabotropic glutamate receptor (increase in Homer 1a and mGlu8), and genes involved in synaptic plasticity. These results suggest that E self-administration produces neuronal alterations that strengthen synaptic function in the Ag. [AA07611, AA13521 (INIA Project), AA13496 (INIA Project), INGEN(R)]

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