The Selective Benefits of Acute Dosing with Dopamine Receptor Agonists on the Visual Function, Cognitive Function, and Blood Glucose Levels in a Rat Model of Type I Diabetes
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Purpose: Previous studies have demonstrated that dopamine D1 and D4 receptor (D1R, D4R) agonists selectively improve spatial frequency and contrast sensitivity thresholds, respectively, in healthy and diabetic mice (Jackson et al., 2012; Aung et al., 2014). The purpose of this experiment was to investigate the selective benefits of three dopamine receptor agonists (D1R, D2R, D4R) on visual function, cognitive function, and blood glucose in a rat model of Type I diabetes with progression of diabetes. Methods: Streptozotocin (STZ) was used to induce hyperglycemia in 2-month-old male Long–Evans rats (n=17). Outcome measures were acquired before and 30 minutes after an intraperitoneal injection of a single dose of a dopamine receptor agonist. Each agonist was injected 2-3 days apart. After 8, 16 and 20 weeks post-STZ, optomotor response (OMR) assessments were conducted. After 10 weeks post-STZ, blood glucose and Y-maze performance were measured on a subset of animals (n=4 diabetics; 6 controls). The spatial frequency, contrast sensitivity, Y-maze performance, and blood glucose for the diabetic rats and control rats post injection were compared to the baseline values to determine the effect of the acute dosing of each dopamine receptor agonist. Results: At the 8, 16, and 20 week timepoints, spatial frequency and contrast sensitivity thresholds were impaired in diabetic animals compared to controls (p<0.0001). At 8 weeks post-STZ, D1R agonist selectively restored spatial frequency thresholds for diabetic rats (p<0.0001), but did not alter thresholds in control rats. At 8 weeks post-STZ, the D4R agonist selectively restored contrast sensitivity thresholds for diabetic rats (p<0.0001) but did not alter thresholds for control rats. The improvements that we observed at 8 weeks in the diabetic animals with the D1R and D4R agonists were no longer observed at 16 or 20 weeks. The D2R agonist did not demonstrate any effects at any timepoint. There was no significant differences in Y-maze and blood glucose values with agonist treatment. Conclusions: Based on these findings, acute dosing of dopamine receptor agonists selectively benefits visual acuity (D1R) and contrast sensitivity (D4R) at early stages of diabetic retinopathy. Thus, dopamine receptor agonists may provide protective treatment options for early stage visual deficits characteristic of Type I diabetes.