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Alcohol Preference (alcohol + preference)

Distribution by Scientific Domains

Medical Sciences	91%
Life Sciences	8%

Selected Abstracts

Ethanol-Responsive Genes (Crtam, Zbtb16, and Mobp) Located in the Alcohol-QTL Region of Chromosome 9 Are Associated With Alcohol Preference in Mice

ALCOHOLISM, Issue 8 2009
Julia Weng
Background:, Previously, our group identified cytotoxic and regulatory T-cell molecule (Crtam), zinc finger and BTB domain containing 16 (Zbtb16), and myelin-associated oligodendrocytic basic protein (Mobp) as ethanol-responsive genes in the mouse brain by gene expression profiling. In this study, we used a genetic co-segregation analysis to assess the association of Crtam, Zbtb16, and Mobp with the alcohol preference (AP) phenotype in the alcohol-preferring C57BL/6J (B6) and alcohol avoiding DBA/2J (D2) strains of mice. Methods:, Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to confirm previous microarray analysis results that Crtam, Zbtb16, and Mobp brain mRNA levels in the B6 and D2 strains are altered by ethanol treatment. The association of the 3 genes with AP was assessed in a F2 population (n = 427) derived from the reciprocal crosses involving the B6 and D2 strains. Each F2 individual was assessed for their AP using the 2 bottle choice test and genotyped for Crtam, Zbtb16, and Mobp single nucleotide polymorphisms (SNPs) that differ between B6 and D2 mice. Results:, Semi-quantitative RT-PCR analysis confirmed that Crtam, Zbtb16, and Mobp are ethanol-responsive genes. The SNP analyses show that alleles of the 3 genes co-segregate with the AP phenotype in F2 mice, where individuals homozygous for the B6 allele have higher AP than those homozygous for the D2 allele. Also, the Crtam,Zbtb16 loci that are tightly linked and the Mobp locus act in an additive fashion in determining the relative AP phenotype. Conclusion:, Our results are consistent with the hypothesis that Crtam, Zbtb16, and Mobp may be involved in AP in mice. The nature of this association remains to be established and may reflect a direct effect of these genes or an indirect effect caused by linked genes on mouse chromosome 9. [source]

Genomewide SNP Screen to Detect Quantitative Trait Loci for Alcohol Preference in the High Alcohol Preferring and Low Alcohol Preferring Mice

ALCOHOLISM, Issue 3 2009
Paula Bice
Background:, The high and low alcohol preferring (HAP1 and LAP1) mouse lines were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice are essentially noninbred lines that originated from the outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice. Methods:, A total of 867 informative SNPs were genotyped in 989 HAP1 × LAP1 F2, 68 F1s, 14 parents (6 LAP1, 8 HAP1), as well as the 8 inbred strains of mice crossed to generate the HS/Ibg colony. Multipoint genome wide analyses were performed to simultaneously detect linked QTLs and also fine map these regions using the ancestral haplotypes. Results:, QTL analysis detected significant evidence of association on 4 chromosomes: 1, 3, 5, and 9. The region on chromosome 9 was previously found linked in a subset of these F2 animals using a whole genome microsatellite screen. Conclusions:, We have detected strong evidence of association to multiple chromosomal regions in the mouse. Several of these regions include candidate genes previously associated with alcohol dependence in humans or other animal models. [source]

Genetic Correlation Between Innate Alcohol Preference and Fear-Potentiated Startle in Selected Mouse Lines

ALCOHOLISM, Issue 7 2007
Gustavo D. Barrenha
Background: There is a high rate of co-occurrence between anxiety and alcohol-use disorders in humans that may arise from the inheritance of common genes that increase the risk for both psychiatric disorders. The purpose of this study was to investigate whether a genetic relationship exists between innate alcohol preference and propensity to develop learned fear, using the fear-potentiated startle (FPS) paradigm, in 2 mouse lines selectively bred for high or low alcohol preference. Methods: Alcohol-naïve, male, and female mice from replicate pairs of lines selectively bred for high alcohol preference and low alcohol preference were randomly assigned to a fear-conditioned or control group. Mice in the fear-conditioned group received 20 pairings of a light stimulus and footshock; the control group received the same number of exposures to light and footshock, except that these stimuli were explicitly unpaired. During testing for FPS, acoustic stimuli were presented both in the presence and in the absence of the light stimulus. Results: In both replicate pairs of lines, mice selectively bred for high alcohol preference showed greater FPS than mice selectively bred for low alcohol preference. No sex differences in FPS were found in any line. Control groups did not show FPS. Conclusion: These findings suggest that common genes mediate both innate alcohol preference and propensity to develop learned fear in these selected mouse lines. [source]

Identification of Candidate Genes for Alcohol Preference by Expression Profiling of Congenic Rat Strains

ALCOHOLISM, Issue 7 2007
Lucinda G. Carr
Background: A highly significant quantitative trait locus (QTL) on chromosome 4 that influenced alcohol preference was identified by analyzing crosses between the iP and iNP rats. Congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP (NP.P) exhibited the expected increase in alcohol consumption compared with the iNP background strain. This study was undertaken to identify genes in the chromosome 4 QTL interval that might contribute to the differences in alcohol consumption between the alcohol-naïve congenic and background strains. Methods: RNA from 5 brain regions from each of 6 NP.P and 6 iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0 microarray to look for both cis -regulated and trans -regulated genes. Expression levels were normalized using robust multi-chip average (RMA). Differential gene expression was validated using quantitative real-time polymerase chain reaction. Five individual brain regions (nucleus accumbens, frontal cortex, amygdala, hippocampus, and striatum) were analyzed to detect differential expression of genes within the introgressed QTL interval, as well as genes outside that region. To increase the power to detect differentially expressed genes, combined analyses (averaging data from the 5 discrete brain regions of each animal) were also carried out. Results: Analyses within individual brain regions that focused on genes within the QTL interval detected differential expression in all 5 brain regions; a total of 35 genes were detected in at least 1 region, ranging from 6 genes in the nucleus accumbens to 22 in the frontal cortex. Analysis of the whole genome detected very few differentially expressed genes outside the QTL. Combined analysis across brain regions was more powerful. Analysis focused on the genes within the QTL interval confirmed 19 of the genes detected in individual regions and detected 15 additional genes. Whole genome analysis detected 1 differentially expressed gene outside the interval. Conclusions: Cis -regulated candidate genes for alcohol consumption were identified using microarray profiling of gene expression differences in congenic animals carrying a QTL for alcohol preference. [source]

Norepinephrine Uptake Sites in the Locus Coeruleus of Rat Lines Selectively Bred for High and Low Alcohol Preference: A Quantitative Autoradiographic Binding Study Using [3H]-Tomoxetine

ALCOHOLISM, Issue 5 2000
Bang H. Hwang
Background: The locus coeruleus (LC) is the largest norepinephrinergic cell group in the central nervous system and contains a high density of norepinephrine (NE) uptake sites. Alcohol-preferring (AP) rats and high,alcohol-drinking (HAD) rats are selectively bred for high alcohol preference, whereas alcohol-nonpreferring (NP) rats and low,alcohol-drinking (LAD) rats are bred for low alcohol preference. However, it is unknown whether NE uptake sites in the LC are associated with alcohol preference in AP and HAD rats when compared with their respective control rats, NP and LAD rats. This study was designed to examine this question. Methods: Animals were decapitated and brains were removed, frozen with dry ice powder, and stored in a deep freezer. The LC tissue blocks were cut into 14 , cryostat sections, collected on glass slides, and incubated with 0.6 nM [3H]-tomoxetine in 50 mM Tris-HCl buffer system. For nonspecific binding, 1 ,M desipramine was added to the radioactive ligand. Sections were rinsed, quickly dried, and processed for quantitative autoradiography. In addition, galanin content in the LC was also studied. Results: The LC possessed a high density of [3H]-tomoxetine binding sites. There were fewer tomoxetine binding sites (fmol/mg protein) in the AP rats (433.0 ± 8.1) than in the NP rats (495.6 ± 3.7). HAD rats (386.5 ± 13.2) also possessed fewer tomoxetine binding sites than LAD rats (458.7 ± 10.1). Galanin content in the LC was similar between AP and NP rats and between HAD and LAD rats. Conclusions: Because both AP rats and HAD rats were selectively bred for alcohol preference, the finding of consistently low levels of [3H]-tomoxetine binding in the LC of these two lines of rats with high alcohol preference suggests that down-regulation of NE transporters in the LC of AP and HAD rats may be associated with alcohol-seeking behavior. A possible involvement of the coerulear NE uptake sites in depression is also discussed. Galanin in the LC may not relate to alcohol preference. [source]

REVIEW: A comparison of selected quantitative trait loci associated with alcohol use phenotypes in humans and mouse models

ADDICTION BIOLOGY, Issue 2 2010
Cindy L. Ehlers
ABSTRACT Evidence for genetic linkage to alcohol and other substance dependence phenotypes in areas of the human and mouse genome have now been reported with some consistency across studies. However, the question remains as to whether the genes that underlie the alcohol-related behaviors seen in mice are the same as those that underlie the behaviors observed in human alcoholics. The aims of the current set of analyses were to identify a small set of alcohol-related phenotypes in human and in mouse by which to compare quantitative trait locus (QTL) data between the species using syntenic mapping. These analyses identified that QTLs for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse chromosome 1 are syntenic to a region on human chromosome 1q where a number of studies have identified QTLs for alcohol-related phenotypes. Additionally, a QTL on human chromosome 15 for alcohol dependence severity/withdrawal identified in two human studies was found to be largely syntenic with a region on mouse chromosome 9, where two groups have found QTLs for alcohol preference. In both of these cases, while the QTLs were found to be syntenic, the exact phenotypes between humans and mice did not necessarily overlap. These studies demonstrate how this technique might be useful in the search for genes underlying alcohol-related phenotypes in multiple species. However, these findings also suggest that trying to match exact phenotypes in humans and mice may not be necessary or even optimal for determining whether similar genes influence a range of alcohol-related behaviors between the two species. [source]

Reduced ethanol response in the alcohol-preferring RHA rats and neuropeptide mRNAs in relevant structures

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006
Marc Guitart-Masip
Abstract Roman rat strains, genetically selected for high (RHA) or low (RLA) active avoidance acquisition in the two-way shuttle box, differ in dopaminergic activity. These two strains appear to be a valid laboratory model of divergent sensation/novelty and substance-seeking profiles. RHA rats show higher ethanol intake and preference than do RLA rats, and it was suggested that RHA rats are more tolerant than RLA to the effects of alcohol. In the hole-board test, we found that the non-alcohol-preferring RLA rats showed enhanced responsiveness to the stimulatory effects of intraperitoneal administration of 0.25 g/kg ethanol when compared with RHA rats. In situ hybridization analysis showed higher levels of preprodynorphin in the accumbens shell and higher levels of preproenkephalin in the cingulate cortex in RHA rats. RLA rats showed higher levels of enkephalin gene transcripts in restricted areas of the dorsal striatum. Finally, differences in cholecystokinin gene transcript, suggestive of a different arrangement of certain interneurons, were found in different cortical areas. The differences in peptide gene expression found between the two strains might reflect the differences in alcohol preference and sensitivity. RHA rats may have more predictive value than other rodent alcoholism models, as high initial tolerance to ethanol is a risk factor for alcoholism in humans. [source]

Identification of genes influencing skeletal phenotypes in congenic P/NP rats

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010
Imranul Alam
Abstract We previously showed that alcohol-preferring (P) rats have higher bone density than alcohol-nonpreferring (NP) rats. Genetic mapping in P and NP rats identified a major quantitative trait locus (QTL) between 4q22 and 4q34 for alcohol preference. At the same location, several QTLs linked to bone density and structure were detected in Fischer 344 (F344) and Lewis (LEW) rats, suggesting that bone mass and strength genes might cosegregate with genes that regulate alcohol preference. The aim of this study was to identify the genes segregating for skeletal phenotypes in congenic P and NP rats. Transfer of the NP chromosome 4 QTL into the P background (P.NP) significantly decreased areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) at several skeletal sites, whereas transfer of the P chromosome 4 QTL into the NP background (NP.P) significantly increased bone mineral content (BMC) and aBMD in the same skeletal sites. Microarray analysis from the femurs using Affymetrix Rat Genome arrays revealed 53 genes that were differentially expressed among the rat strains with a false discovery rate (FDR) of less than 10%. Nine candidate genes were found to be strongly correlated (r2,>,0.50) with bone mass at multiple skeletal sites. The top three candidate genes, neuropeptide Y (Npy), , synuclein (Snca), and sepiapterin reductase (Spr), were confirmed using real-time quantitative PCR (qPCR). Ingenuity pathway analysis revealed relationships among the candidate genes related to bone metabolism involving ,-estradiol, interferon-,, and a voltage-gated calcium channel. We identified several candidate genes, including some novel genes on chromosome 4 segregating for skeletal phenotypes in reciprocal congenic P and NP rats. © 2010 American Society for Bone and Mineral Research [source]

A Critical Evaluation of Influence of Ethanol and Diet on Salsolinol Enantiomers in Humans and Rats

ALCOHOLISM, Issue 2 2010
Jeongrim Lee
Background:, (R/S)-Salsolinol (SAL), a condensation product of dopamine (DA) with acetaldehyde, has been speculated to have a role in the etiology of alcoholism. Earlier studies have shown the presence of SAL in biological fluids and postmortem brains from both alcoholics and nonalcoholics. However, the involvement of SAL in alcoholism has been controversial over several decades, since the reported SAL levels and their changes after ethanol exposure were not consistent, possibly due to inadequate analytical procedures and confounding factors such as diet and genetic predisposition. Using a newly developed mass spectrometric method to analyze SAL stereoisomers, we evaluated the contribution of ethanol, diet, and genetic background to SAL levels as well as its enantiomeric distribution. Methods:, Simultaneous measurement of SAL enantiomers and DA were achieved by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Plasma samples were collected from human subjects before and after banana (a food rich in SAL) intake, and during ethanol infusion. Rat plasma and brain samples were collected at various time points after the administration of SAL or banana by gavage. The brain parts including nucleus accumbens (NAC) and striatum (STR) were obtained from alcohol-non-preferring (NP) or alcohol-preferring (P) rats as well as P-rats which had a free access to ethanol (P-EtOH). Results:, Plasma SAL levels were increased significantly after banana intake in humans. Consistently, administration of banana to rats also resulted in a drastic increase of plasma SAL levels, whereas brain SAL levels remained unaltered. Acute ethanol infusion did not change SAL levels or R/S ratio in plasma from healthy humans. The levels of both SAL isomers and DA were significantly lower in the NAC of P rats in comparison to NP rats. The SAL levels in NAC of P rats remained unchanged after chronic free-choice ethanol drinking. There were decreasing trends of SAL in STR and DA in both brain regions. No changes in enantiomeric ratio were observed after acute or chronic ethanol exposure. Conclusions:, SAL from dietary sources is the major contributor to plasma SAL levels. No significant changes of SAL plasma levels or enantiomeric distribution after acute or chronic ethanol exposure suggest that SAL may not be a biomarker for ethanol drinking. Significantly lower SAL and DA levels observed in NAC of P rats may be associated with innate alcohol preference. [source]

Ethanol Is Self-Administered Into the Nucleus Accumbens Shell, But Not the Core: Evidence of Genetic Sensitivity

ALCOHOLISM, Issue 12 2009
Eric A. Engleman
Background:, A previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the posterior ventral tegmental area at lower concentrations than Wistar rats. The present study was undertaken to determine involvement of the nucleus accumbens (Acb) with EtOH reinforcement, and a relationship between genetic selection for high alcohol preference and sensitivity of the Acb to the reinforcing effects of EtOH. Methods:, Adult P and Wistar rats were assigned to groups that self-infused 0 to 300 mg% EtOH into the Acb shell (AcbSh) or Acb Core (AcbC). Rats were placed into 2-lever (active and inactive) operant chambers and given EtOH for the first 4 sessions (acquisition), artificial cerebrospinal fluid (aCSF) for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate. Results:, Alcohol-preferring rats self-infused 75 to 300 mg% EtOH, whereas Wistar rats reliably self-infused 100 and 300 mg% EtOH into the AcbSh. Both P and Wistar rats reduced responding on the active lever when aCSF was substituted for EtOH, and reinstated responding in session 7 when EtOH was restored. EtOH was not self-infused into the AcbC by P or Wistar rats. Conclusions:, The present results indicate that the AcbSh, but not AcbC, is a neuroanatomical structure that mediates the reinforcing actions of EtOH. The data also suggest that, compared to Wistar rats, the AcbSh of P rats is more sensitive to the reinforcing effects of EtOH. [source]

Increased Perioculomotor Urocortin 1 Immunoreactivity in Genetically Selected Alcohol Preferring Rats

ALCOHOLISM, Issue 11 2009
Irina Fonareva
Introduction:, Urocortin 1 (Ucn 1) is an endogenous peptide related to the corticotropin-releasing factor (CRF). Ucn 1 is mainly expressed in the perioculomotor area (pIII), and its involvement in alcohol self-administration is well confirmed in mice. In other species, the relationship between the perioculomotor Ucn 1-containing population of neurons (pIIIu) and alcohol consumption needs further investigation. The pIII also has a significant subpopulation of dopaminergic neurons. Because of dopamine's (DA) role in addiction, it is important to evaluate whether this subpopulation of neurons contributes to addiction-related phenotypes. Furthermore, the effects of gender on the relationship between Ucn 1 and tyrosine hydroxylase (TH) in pIII and alcohol preference in rats have not been previously assessed. Methods:, To address these issues, we compared 2 Sardinian alcohol-preferring sublines of rats, a population maintained at the Scripps Research Institute (Scr:sP) and a population maintained at University of Camerino,Marchigian Sardinian preferring rats (msP), to corresponding nonselectively bred Wistar rats of both sexes. Ucn 1- and TH-positive cells were detected on coronal midbrain sections from 6- to 8-week-old alcohol-naïve animals using brightfield and fluorescent immunohistochemistry. Ucn 1- and TH-positive cells in pIII were counted in the perioculomotor area, averaged across 2 to 3 sets, and binned into 3 bregma levels. Results:, Results demonstrated increased average counts of Ucn 1-positive cells in the middle bregma level in preferring male rats compared to Wistar controls and no difference in TH-positive cell counts in pIII. In addition, fluorescent double labeling revealed no colocalization of Ucn 1-positive and TH-positive neurons. Ucn 1 but not TH distribution was influenced by gender with female animals expressing more Ucn 1-positive cells than male animals in the peak bregma level. Conclusions:, These findings extend previous reports of increased Ucn 1-positive cell distribution in preferring lines of animals. They indicate that Ucn1 contributes to increased alcohol consumption across different species and that this contribution could be gender specific. The results also suggest that Ucn1 regulates positive reinforcing rather than aversive properties of alcohol and that these effects could be mediated by CRF2 receptors, independent of direct actions of DA. [source]

Blood Glucose Level, Alcohol Heavy Drinking, and Alcohol Craving During Treatment for Alcohol Dependence: Results From the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study

ALCOHOLISM, Issue 9 2009
Lorenzo Leggio
Background:, Heavy drinking may increase blood glucose levels. Moreover, in alcohol-dependent subjects, glucose may play a putative role in alcohol preference. Methods:, This study investigated the relationship between blood glucose levels and both alcohol heavy drinking and craving in alcohol-dependent subjects participating in the COMBINE Study. The primary objective was to evaluate the relationship between baseline (pretreatment) glucose levels and percentage of heavy drinking day (PHDD) during treatment. The secondary objective was to evaluate the relationship between glucose levels, baseline PHDD, and craving measured by the Obsessive Compulsive Drinking Scale (OCDS). Results:, This analysis consisted of 1,324 participants. Baseline glucose levels were significantly and positively associated with PHDD during treatment [F(1, 1225) = 5.21, p = 0.023], after controlling for baseline PHDD [F(1, 1225) = 36.25, p < 0.0001], gender [F (1, 1225) = 3.33, p = 0.07], and body mass index (BMI) [F(1, 1225) = 0.31, p = 0.58]. Higher glucose levels at baseline were associated with a higher percentage of PHDD at pretreatment [F(1, 1304) = 5.96, p = 0.015], after controlling for gender [F(1, 1304) = 0.29, p = 0.59] and BMI [F(1, 1304) = 0.90, p = 0.34]. Glucose was not significantly associated with the OCDS total score [F(1, 1304) = 0.12, p = 0.73], the OCDS Obsessive subscale [F(1, 1304) = 0.35, p = 0.56], or the OCDS Compulsive subscale [F(1, 1304) = 1.19, p = 0.28] scores, after controlling for gender and BMI. Discussion:, A link between pretreatment glucose levels and heavy drinking during treatment was found, suggesting a role of glucose in predicting heavy alcohol consumption. Although caution is needed in the interpretation of these results, elevated glucose and heavy drinking may be affected by a common mechanism and manipulations affecting glucose regulation may influence alcohol consumption. [source]

Ethanol-Responsive Genes (Crtam, Zbtb16, and Mobp) Located in the Alcohol-QTL Region of Chromosome 9 Are Associated With Alcohol Preference in Mice

Alterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission Tomography

ALCOHOLISM, Issue 2 2009
Masami Nishikawa
Background:, A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release. Methods:, The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer ,-[11C]-methyl- l -tryptophan. Results:, Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala. Conclusions:, Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation. [source]

The ,1 -Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol-Preferring (P) Rats

ALCOHOLISM, Issue 2 2009
Dennis D. Rasmussen
Background:, Preliminary evidence suggest that noradrenergic signaling may play a role in mediating alcohol drinking behavior in both humans and rats. Accordingly, we tested the hypothesis that blockade of ,1 -adrenergic receptors will suppress alcohol drinking in rats selectively bred for alcohol preference (P line). Methods:, Adult male P rats were given 24-hour access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2 hours daily. Rats were injected IP with the ,1 -adrenergic receptor antagonist, prazosin (0, 0.5, 1.0, 1.5, or 2.0 mg/kg body weight), once a day at 15 minutes prior to onset of the daily 2-hour 2-bottle choice, alcohol versus water, access period for 2 consecutive days and then 3 weeks later for 5 consecutive days. Results:, Prazosin significantly reduced (p < 0.01) alcohol intake during the initial 2 daily administrations, and this reduction of alcohol intake was maintained for 5 consecutive days by daily prazosin treatment in the subsequent more prolonged trial (p < 0.05). The prazosin-induced reduction of alcohol intake was not dependent upon drug-induced motor impairment since increases in water drinking (p < 0.05) were exhibited during the 2-hour access periods during both 2- and 5-day prazosin treatment. Conclusions:, The results indicate that the noradrenergic system plays a role in mediating alcohol drinking in rats of the P line and suggest that prazosin,a safe, well-characterized, and well-tolerated drug,may be an effective pharmacotherapeutic agent for the treatment of alcohol use disorders. [source]

Innate Differences in the Expression of Brain-Derived Neurotrophic Factor in the Regions Within the Extended Amygdala Between Alcohol Preferring and Nonpreferring Rats

ALCOHOLISM, Issue 6 2008
Anand Prakash
Background:, Animal lines such as alcohol-preferring (P) and nonpreferring (NP) rats appear to be suitable animal models to investigate the biological basis of alcohol-drinking behaviors. The extended amygdala serves as a neuroanatomical substrate for alcohol-drinking behaviors. Brain-derived neurotrophic factor (BDNF) in the amygdala has been implicated in alcohol-drinking behaviors; however, its expression in the extended amygdala of P and NP rats is unknown. Therefore, we examined the basal expression of BDNF in the extended amygdala of alcohol naïve P and NP rats. Methods:, We determined the basal mRNA and protein levels of BDNF by in situ RT-PCR and immuno-histochemical procedure, respectively, in the amygdaloid [central nucleus of amygdala (CeA), medial nucleus of amygdala (MeA), and basolateral amygdala (BLA)], nucleus accumbal (NAc shell and core), and bed nucleus of stria terminalis (BNST) [lateral BNST (lBNST), medial BNST (mBNST), and ventral BNST (vBNST)] brain structures of P and NP rats. In addition, we examined the localization of BDNF in neurons using double-immunofluorescence labeling of BDNF with neuron-specific nuclear protein (NeuN) and also determined the number of NeuN-positive neurons in the amygdaloid structures of P and NP rats. Results:, The mRNA and protein levels of BDNF were found to be significantly lower in both the CeA and MeA, but not in the BLA, of P compared with NP rats. We also found that BDNF was expressed in neurons in the amygdaloid structures of P and NP rats. In addition, we found that the number of NeuN-positive neurons was similar in the amygdaloid structures of P and NP rats. Interestingly, the mRNA and protein levels of BDNF were also significantly lower in the lBNST, mBNST, and vBNST of P compared with NP rats. On the other hand, mRNA and protein levels of BDNF were similar in the NAc shell and core structures of P and NP rats. Conclusions:, P and NP rats are selectively bred for higher and lower alcohol preference, respectively; therefore it is possible that lower BDNF levels in the amygdaloid and BNST structures may be associated with the excessive alcohol-drinking behaviors of P rats. [source]

Ethanol Preference Is Inversely Correlated With Ethanol-Induced Dopamine Release in 2 Substrains of C57BL/6 Mice

ALCOHOLISM, Issue 10 2007
Vorani Ramachandra
Background:, The C57BL/6 mouse model has been used extensively in alcohol drinking studies, yet significant differences in ethanol preference between substrains exist. Differences in ethanol-induced dopamine release in the ventral striatum could contribute to this variability in drinking behavior as dopamine has been implicated in the reinforcing properties of ethanol. Methods:, A 2-bottle choice experiment investigated the difference in ethanol preference between C57BL/6J and C57BL/6NCrl animals. Microdialysis was used to determine dopamine release and ethanol clearance in these 2 substrains after intraperitoneal injections of 1.0, 2.0 and 3.0 g/kg ethanol or saline. Results:, C57BL/6J mice exhibited significantly greater ethanol preference and less ethanol-stimulated dopamine release compared with C57BL/6NCrl mice. The intraperitoneal injections of ethanol caused a significant increase in dopamine in both substrains at all 3 doses with significant differences between substrains at the 2 highest alcohol doses. Saline injections had a significant effect on dopamine release when given in a volume equivalent to the 3 g/kg ethanol dose. Ethanol pharmacokinetics were similar in the 2 substrains at all 3 doses. Conclusions:, Ethanol-induced dopamine release in the ventral striatum may contribute to the differences in alcohol preference between C57BL/6J and C57BL/6NCrl mice. [source]

Genetic Correlation Between Innate Alcohol Preference and Fear-Potentiated Startle in Selected Mouse Lines

Identification of Candidate Genes for Alcohol Preference by Expression Profiling of Congenic Rat Strains

Aldehyde Dehydrogenase 2 Gene Targeting Mouse Lacking Enzyme Activity Shows High Acetaldehyde Level in Blood, Brain, and Liver after Ethanol Gavages

ALCOHOLISM, Issue 11 2005
Toyohi Isse
Abstract: Background: Previously, we created an aldehyde dehydrogenase 2 gene transgenic (Aldh2,/,) mouse as an aldehyde dehydrogenase (ALDH) 2 inactive human model and demonstrated low alcohol preference. In addition, after a free-choice drinking test, no difference in the acetaldehyde level was observed between the Aldh2,/, and wild type (Aldh2+/+) mice. The actual amounts of free-choice drinking were so low that it is uncertain whether these levels are pharmacologically and/or behaviorally relevant in either strain. To elucidate this uncertainty, we compared the ethanol and acetaldehyde concentration in the blood, brain, and liver between the Aldh2,/, and Aldh2+/+ mice after ethanol gavages at the same dose and time. Method: We measured differences in the ethanol and acetaldehyde levels between the Aldh2,/, and Aldh2+/+ mice by headspace gas chromatography-mass spectrometry (GC-MS) after ethanol gavages at the same dose and time. Results: Significantly higher blood acetaldehyde concentrations were found in the Aldh2,/, mice than in the Aldh2+/+ mice 1 hr after the administration of ethanol gavages at doses of 0.5, 1.0, 2.0, and 5.0 g/kg. The blood acetaldehyde concentrations in the two strains were 2.4 vs. 0.5, 17.8 vs. 1.9, 108.3 vs. 4.3, and 247.2 vs. 14.0 (,M), respectively. In contrast, no significant difference was observed in the blood ethanol concentrations between the Aldh2+/+ and Aldh2,/, mice. The aldehyde dehydrogenase 2 enzyme metabolized 94% of the acetaldehyde produced from the ethanol as calculated from the area under the curve (AUC) of acetaldehyde when ethanol was administered at a dose of 5.0 g/kg. Conclusions: These data indicate that mouse ALDH2 is a major enzyme for acetaldehyde metabolism, and the Aldh2,/, mice have significantly high acetaldehyde levels after ethanol gavages. [source]

The Expression of an Alcohol Deprivation Effect in the High,Alcohol-Drinking Replicate Rat Lines Is Dependent On Repeated Deprivations

ALCOHOLISM, Issue 6 2000
Zachary A. Rodd-Henricks
Background: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH) solutions over baseline drinking conditions when EtOH access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. In the current study, we examined the effects of initial deprivation length and number of deprivation exposures on the ADE in the replicate lines of the high,alcohol-drinking (HAD) rats. Methods: Adult male HAD-1 and HAD-2 rats received 24 hr free-choice access to 10% (v/v) EtOH and water for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control), or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2 weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of access and 2 weeks of deprivation was carried out for a total of four deprivations. Results: After the initial EtOH deprivation period, EtOH consumption in HAD-1 and HAD-2 rats returned to baseline levels but failed to exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE was observed in two of the four deprived groups for the HAD-1 rats (2 week and 6 week groups) and in all deprived groups for the HAD-2 rats after a second deprivation, and in all deprived groups of both lines after a third deprivation. In the HAD-2 line, but not in the HAD-1 line, the duration of the ADE was prolonged into the second reinstatement day after the fourth deprivation. Conclusions: The expression of an ADE was observed only after repeated deprivation periods in the HAD lines. The duration of the ADE was prolonged in the HAD-2 line, but not in the HAD-1 line, with repeated deprivations, which suggests a dissociation between selection for alcohol preference and the effects of repeated deprivations on the duration of the ADE. [source]

Norepinephrine Uptake Sites in the Locus Coeruleus of Rat Lines Selectively Bred for High and Low Alcohol Preference: A Quantitative Autoradiographic Binding Study Using [3H]-Tomoxetine