期刊
FASEB JOURNAL
卷 22, 期 8, 页码 2740-2746出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.08-110759
关键词
body weight; nucleus accumbens; striatum; prefrontal cortex; vesicular monoamine transporter 2; tyrosine hydroxylase
资金
- NIDA NIH HHS [DA023760, F31 DA023760] Funding Source: Medline
- NIDDK NIH HHS [R01 DK065872, DK065872, P30 DK34928, P30 DK034928] Funding Source: Medline
- NINDS NIH HHS [P30 NS047243] Funding Source: Medline
The association between dietary obesity and mesolimbic systems that regulate hedonic aspects of feeding is currently unresolved. In the present study, we examined differences in baseline and stimulated central dopamine levels in obesity-prone (OP) and obesity-resistant ( OR) rats. OP rats were hyperphagic and showed a 20% weight gain over OR rats at wk 15 of age, when fed a standard chow diet. This phenotype was associated with a 50% reduction in basal extracellular dopamine, as measured by a microdialysis probe in the nucleus accumbens, a projection site of the mesolimbic dopamine system that has been implicated in food reward. Similar defects were also observed in younger animals ( 4 wk old). In electrophysiology studies, electrically evoked dopamine release in slice preparations was significantly attenuated in OP rats, not only in the nucleus accumbens but also in additional terminal sites of dopamine neurons such as the accumbens shell, dorsal striatum, and medial prefrontal cortex, suggesting that there may be a widespread dysfunction in mechanisms regulating dopamine release in this obesity model. Moreover, dopamine impairment in OP rats was apparent at birth and associated with changes in expression of several factors regulating dopamine synthesis and release: vesicular monoamine transporter-2, tyrosine hydroxylase, dopamine transporter, and dopamine receptor-2 short-form. Taken together, these results suggest that an attenuated central dopamine system would reduce the hedonic response associated with feeding and induce compensatory hyperphagia, leading to obesity.
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