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

Overview

Journal Biol Psychiatry

Publisher Elsevier

Specialty Psychiatry

Date 2024 Oct 12

PMID 39395473

Authors

Patrick D Worhunsky

Marcella M Mignosa

Jean-Dominique Gallezot

Brian Pittman

Nabeel B Nabulsi

Adam Stryjewski

Laya Jalilian-Khave

Richard Trinko

Ralph J DiLeone

Richard E Carson

Robert T Malison

Marc N Potenza

Gustavo A Angarita

Affiliations

Soon will be listed here.

Abstract

Background: Dopaminergic tone and phasic release have transdiagnostic relevance. Preclinical research suggests that the active form of vitamin D, calcitriol, increases subcortical tyrosine hydroxylase, D/D 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) [C]-PHNO positron emission tomography scanning to examine D/D receptor availability (nondisplaceable binding potential [BP]) 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 [C]-PHNO positron emission tomography BP 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 (F = 2.59, p = .039) and a main effect of medication (F = 4.88, p = .029) on BP, with higher BP values on calcitriol in the ventral striatum (t = 2.89, p = .004) and dorsal putamen (t = 2.15, p = .033). There was a main effect of medication on postamphetamine change in BP (F = 5.93, p = .016), with greater decreases in calcitriol in the ventral striatum (t = 3.00, p = .003), substantia nigra (t = 2.49, p = .014), and dorsal caudate (t = 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.

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