2007 Fiscal Year Final Research Report Summary
Neuropharmacological studies of habitual alcohol drinking behavior in animal models
| Project/Area Number |
17390203
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
YOSHIMOTO Kanii Kyoto Prefectural University of Medicine, Graduate School of Medicine Department of Legal Medicine, Associate Professor (70111903)
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| Co-Investigator(Kenkyū-buntansha) |
YASUHARA Masahiro Kyoto Prefectural University of Medicine, Department of Legal Medicine, Professor (60305604)
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| Project Period (FY) |
2005 – 2007
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| Keywords | uncoupling protein / ethanol / RNA / 5-HT receptor / nucleus accumbens / mice |
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| Research Abstract |
Alcohol drinking behavior results from an intricate interplay between genes and environmetal factors, but there remains little understanding of how drinking onset and housing conditions interact to influence on late alcohol drinking behavior. Expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT) was studied in young and rats. Mitocondrial UCP1 in BAT is an important key molecule for non-shivering thermogenesis. IP injection of EtOH (2g/kg) caused a decreased expression of BAT UCP1 mRNA in both young and aged rats, but the magnitude of UCP1 mRNA decrease was larger in aged rats than in young rats. Alcohol drinking behavior depends on age of drinking onset and the sensitivity to alcohol associated with functions of ACC DA and 5-HT releases during the process of aging. Mice were injected s.c. with 5, 10 and 20 mg/kg mCPP for 15 days, respectively. Daily intakes of water and 10% ethanol were measured to evaluate alcohol preference (AP) (%) and an alcohol consumption score (g/kg/day).The levels of dopamine (DA) and serotonin (5-H')were analyzed by ECD-HPLC in. the frontal cortex (FC), lateral hypothalamus (LH) and striatum (C/P). MCPP increased AP in a dose-dependently manner. Positive and negative relationships were noted between alcohol consumption score and food intake and mCPP, respectively. MCPP (20mg/kg) increased the level of DA in LH and C/P. The relationship between the levels of 5-HT and mCPP showed a positive correlation in the LH and C/P. The ratios of DOPAC/DA and 5-HIAA/5-HT showed negative correlations with mCPP. It was suggested that the development of alcohol dependence was associated with the down-regulation of 5-HT2c receptor function.
Possible underlying reasons for different alcohol drinking behavior in adults include reduced sensitivity to alcohol in the rewarding system and altered responses of the autonomic nerves associated with 5-HT2 receptor functions, e.g., energy dissipation and the stress of housing conditions.
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