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Evidence for defective mesolimbic dopamine exocytosis in obesity‐prone rats
Author(s) -
Geiger Brenda M.,
Behr Gerald G.,
Frank Lauren E.,
Caldera-Siu Angela D.,
Beinfeld Margery C.,
Kokkotou Efi G.,
Pothos Emmanuel N.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-110759
Subject(s) - nucleus accumbens , dopamine , endocrinology , dopamine transporter , medicine , microdialysis , catecholamine , striatum , ventral striatum , chemistry , neuroscience , biology , dopaminergic
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.—Geiger, B. M., Behr, G. G., Frank, L. E., Caldera‐Siu, A. D., Beinfeld, M. C., Kokkotou, E. G., Pothos, E. N. Evidence for defective mesolimbic dopamine exocytosis in obesity‐prone rats. FASEB J. 22, 2740–2746 (2008)