Striatal Dopamine Release in Response to Morphine: A [C]Raclopride Positron Emission Tomography Study in Healthy Men

Overview

Journal Biol Psychiatry

Publisher Elsevier

Specialty Psychiatry

Date 2019 May 18

PMID 31097294

Citations 18

Authors

Primavera A Spagnolo

Alane Kimes

Melanie L Schwandt

Ehsan Shokri-Kojori

Shantalaxmi Thada

Karran A Phillips

Nancy Diazgranados

Kenzie L Preston

Peter Herscovitch

Dardo Tomasi

Vijay A Ramchandani

Markus Heilig

Affiliations

Soon will be listed here.

Abstract

Background: Preclinical and human positron emission tomography studies have produced inconsistent results regarding the effects of opioids on mesolimbic dopamine (DA). Here, we quantify striatal DA release (measured by [C]raclopride displacement) in response to an intravenous infusion of morphine, and its relationship with morphine-induced subjective effects, in healthy, nondependent opioid-experienced participants.

Methods: Fifteen healthy male participants were initially included. Sessions were on separate days. On session 1, participants received intravenous morphine (10 mg/70 kg) in the clinic to ensure tolerability. Participants without adverse reactions (n = 10) then received intravenous morphine and placebo (saline) sessions, in counterbalanced order, while undergoing [C]raclopride positron emission tomography scans. Subjective and physiological responses were assessed. Region-of-interest and voxelwise image analyses were used to assess changes in [C]raclopride nondisplaceable binding potential.

Results: Morphine produced marked subjective and physiological effects and induced a significant decrease in [C]raclopride nondisplaceable binding potential, particularly in the nucleus accumbens and globus pallidus, where the change in [C]raclopride nondisplaceable binding potential was approximately 9%. However, the subjective effects of morphine did not show a simple pattern of correlation with DA release.

Conclusions: This is, to our knowledge, the first study providing in vivo human evidence that DA transmission in the ventral striatum is affected by morphine. Further studies are required to fully delineate the DA contribution to the reinforcing effects of opioids.

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