Reduced insulin sensitivity is related to less endogenous dopamine at D_2/3 receptors in the ventral striatum of healthy nonobese humans

Background: Food addiction is a debated topic in neuroscience. Evidence suggests diabetes is related to reduced basal dopamine levels in the nucleus accumbens, similar to persons with drug addiction. It is unknown whether insulin sensitivity is related to endogenous dopamine levels in the ventral striatum of humans. We examined this using the agonist dopamine D_2/3 receptor radiotracer [¹¹C]-(+)-PHNO and an acute dopamine depletion challenge. In a separate sample of healthy persons, we examined whether dopamine depletion could alter insulin sensitivity. Methods: Insulin sensitivity was estimated for each subject from fasting plasma glucose and insulin using the Homeostasis Model Assessment II. Eleven healthy nonobese and nondiabetic persons (3 female) provided a baseline [11C]-(+)-PHNO scan, 9 of which provided a scan under dopamine depletion, allowing estimates of endogenous dopamine at dopamine D_2/3 receptor. Dopamine depletion was achieved via alpha-methyl-para-tyrosine (64 mg/kg, P<O.). In 25 healthy persons (9 female), fasting plasma and glucose was acquired before and after dopamine depletion. Results: Endogenous dopamine at ventral striatum dopamine D_2/3 receptor was positively correlated with insulin sensitivity (r(7) =.84, P =.005) and negatively correlated with insulin levels (r(7) =-.85, P =.004). Glucose levels were not correlated with endogenous dopamine at ventral striatum dopamine D_2/3 receptor (r(7) =-.49, P =.18). Consistently, acute dopamine depletion in healthy persons significantly decreased insulin sensitivity (t(24) = 2.82, P =.01), increased insulin levels (t(24) =-2.62, P = 01), and did not change glucose levels (t(24) =-0.93, P = 36). Conclusion: In healthy individuals, diminished insulin sensitivity is related to less endogenous dopamine at dopamine D_2/3 receptor in the ventral striatum. Moreover, acute dopamine depletion reduces insulin sensitivity. These findings may have important implications for neuropsychiatric populations with metabolic abnormalities.