Vitamin D's Capacity to Increase Amphetamine-Induced Dopamine Release in Healthy Humans: A Clinical Translational [11C]-PHNO Positron Emission Tomography Study.

BACKGROUND

Dopaminergic tone and phasic release have transdiagnostic relevance. Preclinical research suggests that the active form of vitamin D, calcitriol, increases subcortical tyrosine hydroxylase, D2/D3 receptors, and amphetamine-stimulated dopamine release in rodents. Comparable studies have not been conducted in humans.

METHODS

Healthy, vitamin D-sufficient adults (N = 18, 32.8 ± 6.6 years; 33% female) participated in a randomized, double-blind, placebo-controlled within-subjects study involving 4 total scans over 2 visits consisting of same-day preamphetamine and postamphetamine (0.3 mg/kg) [11C]-PHNO positron emission tomography scanning to examine D2/D3 receptor availability (nondisplaceable binding potential [BPND]) following active calcitriol (1.5 μg night before experimental day and 1.5 μg morning of experimental day) or placebo at least 6 days apart. Parametric images of [11C]-PHNO positron emission tomography BPND were computed using a simplified reference tissue model with the cerebellum as reference. Blood samples were acquired to measure serum calcitriol, amphetamine, and calcium levels. Regions of interest examined were the dorsal caudate, dorsal putamen, ventral striatum, globus pallidus, and substantia nigra.

RESULTS

For preamphetamine scans, there was a medication × region of interest interaction (F4,153 = 2.59, p = .039) and a main effect of medication (F1,153 = 4.88, p = .029) on BPND, with higher BPND values on calcitriol in the ventral striatum (t153 = 2.89, p = .004) and dorsal putamen (t153 = 2.15, p = .033). There was a main effect of medication on postamphetamine change in BPND (F4,153 = 5.93, p = .016), with greater decreases in calcitriol in the ventral striatum (t153 = 3.00, p = .003), substantia nigra (t153 = 2.49, p = .014), and dorsal caudate (t153 = 2.29, p = .023).

CONCLUSIONS

Results provide translational support for vitamin D to target dopaminergic tone, with implications for clinical disorders that involve dysregulated dopamine function.