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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Altered basal and stimulated accumbens dopamine release in obese OLETF rats as a function of age and diabetic status

¹Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey; and ²Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania

Submitted 27 April 2007 ; accepted in final form 4 June 2007

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is hyperphagic, prefers palatable and high-calorie meals, and gradually develops obesity and type 2 diabetes. To determine dopamine levels in this strain, we used in vivo quantitative (no net flux) microdialysis at three different ages representing nondiabetic (8 wk), prediabetic (18 wk), and diabetic (56 wk) stages in OLETF and age-matched lean Long-Evans Tokushima Otsuka (LETO) controls. Results showed significantly elevated basal dopamine levels in the caudomedial nucleus accumbens of OLETF rats compared with LETO at younger ages (8 wk: 20.10 ± 5.61 nM vs. 15.85 ± 5.63 nM; 18 wk: 7.37 ± 3.71 nM vs. 4.75 ± 1.25 nM, means ± SD). In contrast, at 56 wk 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-wk-old OLETF compared with 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 with LETO across all age groups with an accentuated strain difference at 56 wk. 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.

obesity; CCK-1 receptor; type 2 diabetes; overeating; no-net-flux microdialysis

This article has been cited by other articles:

				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]