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1 Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, United States
2 Nutritional Sciences, The Pennsylvania State University, College of Medicine, College of Human Health and Development, University Park, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: ahajnal{at}psu.edu.
The Otsuka Long Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is hyperphagic, prefers palatable and high caloric meals, and gradually develops obesity and type-2 diabetes. To determine dopamine levels in this strain, we used in-vivo quantitative (no-net flux) microdialyis at three different ages representing non-diabetic (8 weeks), pre-diabetic (18 weeks), and diabetic (56 weeks) stages in OLETF and age-matched lean LETO controls. Results showed significantly elevated basal dopamine levels in the caudomedial nucleus accumbens of OLETF rats compared to LETO at younger ages (8 weeks: 20.10 ± 5.61 nM vs. 15.85 ± 5.63 nM; 18 weeks: 7.37 ± 3.71 nM vs. 4.75 ± 1.25 nM, Mean ± SD). In contrast, at 56 weeks of age, a profound decline in extracellular dopamine concentrations was seen in both strains with a tendency for a greater effect in OLETF rats (1.78 ± 0.40 nM vs. 2.39 ± 0.42 nM). Further, extracellular fraction, an index for reuptake, was higher in 56-week old OLETF compared to LETO (0.648 ± 0.049 vs. 0.526 ± 0.057). Potassium-stimulated dopamine efflux revealed an increased capacity of vesicular pool in OLETF rats compared to LETO across all age groups with an accentuated strain difference at 56 weeks. These findings demonstrate altered striatal dopamine functions (i.e. increased stimulated release and uptake) in obese OLETF rat. This could be due to the lack of functional CCK-1 receptors, or metabolic and hormonal factors associated with the development of obesity and insulin resistance, or both.
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A. Hajnal, N. K. Acharya, P. S. Grigson, M. Covasa, and R. C. Twining Obese OLETF rats exhibit increased operant performance for palatable sucrose solutions and differential sensitivity to D2 receptor antagonism Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1846 - R1854. [Abstract] [Full Text] [PDF] |
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