| 1. |
- Landgren, Sara, 1980, et al.
(författare)
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Expression of the gene encoding the ghrelin receptor in rats selected for differential alcohol preference.
- 2011
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Ingår i: Behavioural brain research. - : Elsevier BV. - 1872-7549 .- 0166-4328. ; 221:1, s. 182-8
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms involved in alcohol use disorder, a chronic relapsing brain disorder, are complex and involve various signalling systems in the brain. Recently, the orexigenic peptide ghrelin was shown to be required for alcohol-induced reward, an effect mediated via ghrelin receptors, GHS-R1A, at the level of the cholinergic-dopaminergic reward link. Moreover, ghrelin increases and GHR-R1A antagonists reduce moderate alcohol consumption in mice, and a single nucleotide polymorphism in the GHS-R1A gene has been associated with high alcohol consumption in humans. Therefore, GHS-R1A gene expression and alcohol intake were investigated in high, AA (Alko, Alcohol), versus low, ANA (Alko, Non-Alcohol), alcohol consuming rats as well as in Wistar rats. In the AA and ANA rats plasma ghrelin levels were also measured. GHS-R1A gene expression was increased in AA compared to ANA rats in nucleus accumbens, ventral tegmental area, amygdala, prefrontal cortex and hippocampus. A similar trend was observed in the ventral tegmental area of Wistar rats consuming high amounts of alcohol. Furthermore, the AA rats had significantly smaller reduction of plasma ghrelin levels over time, after several weeks of alcohol exposure, than had the ANA rats. The present study provides further evidence for that the ghrelin signalling system, in particular at the level of the mesocortocolimbic dopamine system, is involved in alcohol consumption, and thus possibly contributes to alcohol use disorder. Therefore the GHS-R1A may constitute a novel candidate for development of new treatment strategies for alcohol dependence.
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| 2. |
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| 3. |
- Oreland, Sadia, et al.
(författare)
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Does the transcription factor AP-2beta have an impact on the genetic and early environmental influence on ethanol consumption?
- 2010
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 117:9, s. 1077-1081
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Tidskriftsartikel (refereegranskat)abstract
- Genes involved in alcoholism have consensus sites for the transcription factor activator protein (TFAP) 2beta. In the present study, we investigated TFAP-2beta protein levels in the ethanol-preferring alko, alcohol (AA) and the ethanol-avoiding alko, non-alcohol (ANA) rat lines. Furthermore, basal and ethanol-induced TFAP-2beta levels were examined in Wistar rats exposed to different early postnatal environments that are known to affect later ethanol consumption. Taken together, we found differences in brainstem TFAP-2beta protein between the AA and ANA rats.
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| 4. |
- Ploj, Karolina, et al.
(författare)
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Effects of melanocortin receptor ligands on ethanol intake and opioid peptide levels in alcohol-preferring AA rats
- 2002
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Ingår i: Brain Research Bulletin. - 0361-9230 .- 1873-2747. ; 59:2, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- Melanocortin (MC) peptides are suggested to play a role in opiate dependence, where they antagonise the addictive properties of opiates. To further study the involvement of the MCs in drug dependence, we analysed the effects of the MC(4)-receptor antagonist HS014 (1 nmol/rat), and the non-selective MC-receptor agonist MTII (1 nmol/rat), using i.c.v. administration, on ethanol intake in alcohol-preferring AA rats. The rats had access to ethanol during 40 days, resulting in a mean ethanol intake of 6.6 g/kg/day, before treatment. One group received only artificial cerebrospinal fluid solution. MTII caused a reduction in ethanol intake and ethanol preference, whereas HS014 was without effect. No effect on water intake was observed. A decrease in food intake was detected after MTII, whereas HS014 induced an increase in food intake. Analysis of dynorphin B and Met-enkephalin-Arg(6)Phe(7) immunoreactive levels revealed that MTII and HS014 altered opioid peptide levels in several brain areas and the pituitary gland of the rats with an established ethanol intake. This is the first report showing that manipulation of the MC-receptor system changes ethanol intake in chronically ethanol-drinking AA rats. In addition, manipulation of the MC system modulates ethanol-induced changes in opioid peptide levels.
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| 5. |
- Roman, Erika, et al.
(författare)
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Behavioral profiling of multiple pairs of rats selectively bred for high and low alcohol intake using the MCSF test
- 2012
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 17:1, s. 33-46
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Tidskriftsartikel (refereegranskat)abstract
- Genetic aspects of alcoholism have been modeled using rats selectively bred for extremes of alcohol preference and voluntary alcohol intake. These lines show similar alcohol drinking phenotypes but have different genetic and environmental backgrounds and may therefore display diverse behavioral traits as seen in human alcoholics. The multivariate concentric square field™ (MCSF) test is designed to provoke exploration and behaviors associated with risk assessment, risk taking and shelter seeking in a novel environment. The aim was to use the MCSF to characterize behavioral profiles in rat lines from selective breeding programs in the United States (P/NP, HAD1/LAD1, HAD2/LAD2), Italy (sP/sNP) and Finland (AA/ANA). The open field and elevated plus maze tests were used as reference tests. There were substantial differences within some of the pairs of selectively bred rat lines as well as between all alcohol-preferring rats. The most pronounced differences within the pairs of lines were between AA and ANA rats and between sP and sNP rats followed by intermediate differences between P and NP rats and minor differences comparing HAD and LAD rats. Among all preferring lines, P, HAD1 and HAD2 rats shared similar behavioral profiles, while AA and sP rats were quite different from each other and the others. No single trait appeared to form a common 'pathway' associated with a high alcohol drinking phenotype among all of the alcohol-preferring lines of rats. The marked behavioral differences found in the different alcohol-preferring lines may mimic the heterogeneity observed among human alcoholic subtypes.
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| 6. |
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| 7. |
- Roman, Erika, et al.
(författare)
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Maternal separation alters acquisition of ethanol intake in male ethanol-preferring AA rats
- 2003
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Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 27:1, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prolonged daily maternal separation can increase the risk for developing substance abuse, whereas brief maternal separation has been reported to induce positive behavioral effects, decrease voluntary ethanol intake and induce long-lasting changes in brain opioid peptides. The ethanol-preferring AA (Alko, Alcohol) rats have altered basal levels of endogenous opioid peptides that may relate to their high voluntary ethanol intake. The purpose of this study was to investigate whether maternal separation could affect acquisition of ethanol intake in AA rats. METHODS: The rat pups were exposed to 15 min (MS15) or 360 min (MS360) of maternal separation during postnatal day 1-21, while control rats were exposed to normal animal facility rearing. As adults, the male rats were gradually introduced to increasing concentrations of ethanol. Furthermore, the effect of restraint stress on voluntary ethanol intake was investigated. RESULTS: The MS15 rats reached a high voluntary ethanol intake later than MS360 and control rats. The MS15 rats had a lower ethanol intake and preference at 8% ethanol compared to MS360 rats and lower ethanol intake compared to control rats. MS15 rats also had a lower 10% ethanol intake in comparison with MS360 rats. Restraint stress decreased the ethanol intake in MS15 and MS360 rats, whereas the ethanol intake in control rats was unaffected. CONCLUSIONS: We have previously shown that prolonged periods of maternal separation in Wistar rats result in an increased ethanol intake later in life. This was not repeated in this study, using AA rats with an inherent high ethanol intake. However, it is shown that brief maternal separation can delay acquisition of high ethanol intake and in addition decrease voluntary ethanol intake and preference in AA rats. Maternal separation for 15 min is therefore suggested to protect against high voluntary ethanol intake later in life.
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| 8. |
- Roman, Erika, et al.
(författare)
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Short and prolonged periods of maternal separation and voluntary ethanol intake in male and female ethanol-preferring AA and ethanol-avoiding ANA rats
- 2005
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Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 29:4, s. 591-601
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic as well as environmental factors can affect the propensity for psychopathology and/or drug dependence. Maternal separation represents an animal experimental model that is useful in studies of effects of early life experiences. The authors have established a protocol for short and prolonged periods of maternal separation to study adult neurochemistry, behavior, and ethanol intake and have previously reported alterations in ethanol intake in Wistar rats and ethanol-preferring rats. The aim of the current study was to more thoroughly study how early life experiences affect an inherited propensity for high and low ethanol intake, respectively, in male and female ethanol-preferring AA (Alko alcohol) and ethanol-avoiding ANA (Alko, Non-Alcohol) rats. METHODS: AA and ANA pups were assigned to one of three different rearing conditions: 15 min (MS15) or 360 min (MS360) of daily maternal separation in litters or normal animal facility rearing (AFR) during postnatal days 1 to 21. In adulthood, voluntary ethanol intake was investigated using the two-bottle free choice paradigm. RESULTS: In male ethanol-preferring AA rats, MS15 resulted in a lower intake and fewer high-preferring animals at 8% and 10% ethanol compared with MS360 rats. The male MS360 rats had a higher ethanol intake at 8% and 10% ethanol in comparison with AFR rats. In contrast, the female AA MS15 and MS360 rats had a lower ethanol intake and a lower preference for the 10% ethanol solution compared with the female AA AFR rats. In male and female ANA rats, no major separation-induced effects were found. CONCLUSIONS: The current results show that genetic inheritance can be affected by environmental manipulations in AA rats with an inherent high ethanol intake. The findings in female ethanol-preferring AA rats give further evidence of a differential outcome of maternal separation in male and female rats, as previously shown.
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| 9. |
- Roman, Erika, et al.
(författare)
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The multivariate concentric square field test reveals different behavioural profiles in male AA and ANA rats with regard to risk taking and environmental reactivity
- 2007
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 183:2, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present investigation was to compare the behavioural profiles in alcohol-preferring AA (Alko, alcohol) and alcohol-avoiding ANA (Alko, non-alcohol) rats. Twelve adult, alcohol-naive male AA and ANA rats were tested in the recently established multivariate concentric square field (MCSF) test. The more traditional open field and elevated plus-maze tests were used as reference tests. Six weeks after the initial MCSF test, a repeated testing was used to explore differences in acquired recognition after a previous experience. The results revealed distinct differences between the two lines. The ANA rats were generally more active in the three tests. In the MCSF, parameters of risk taking and shelter seeking indicated differences between the two lines. The ANA rats had higher shelter seeking behaviour and less risk taking behaviour than the AA rats. Repeated exposure to the MCSF caused a general decrease in activity and reduction in the number of visits to the various zones, especially evident in the ANA rats. The ANA rats showed more shelter seeking than the AA rats and also more shelter seeking than in the first trial, supporting an "anxiety-like" profile in these rats. In conclusion, the parameters related to risk taking and shelter seeking revealed obvious differences between AA and ANA rats. The higher risk taking behaviour seen in the AA rats might relate to their innate propensity for high voluntary alcohol intake. The results are discussed in relation to the reported neurobiological differences and in relation to other alcohol-preferring and alcohol-avoiding rat lines.
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