Striatal Dopamine Release in Response to Morphine: A [11C]Raclopride Positron Emission Tomography Study in Healthy Men

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 [11C]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 [11C]raclopride positron emission tomography scans. Subjective and physiological responses were assessed. Region-of-interest and voxelwise image analyses were used to assess changes in [11C]raclopride nondisplaceable binding potential.

Results: Morphine produced marked subjective and physiological effects and induced a significant decrease in [11C]raclopride nondisplaceable binding potential, particularly in the nucleus accumbens and globus pallidus, where the change in [11C]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.

Trial registration: ClinicalTrials.gov NCT01878006.

Keywords: Dopamine; Morphine; Opioids; PET; Ventral striatum; [(11)C]Raclopride.

Conflict of interest statement

Disclosures

The authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2019 Society of Biological Psychiatry. All rights reserved.

Figures

Figure 1.

Subjective responses to morphine and placebo outside the scanner environment (Visit 1) on the DEQ. Injection of morphine produced significant condition x time interactions on ‘feel high’ (F[6,56] = 11.52, p

Figure 2.

Subjective responses to morphine and placebo inside the scanner environment (Visit 2 and 3) on the DEQ. Injection of morphine produced significant condition x time interactions on ‘feel high’ (F[6,51] = 31.19, p

Figure 3.

Changes in [11C]-raclopride binding potential (BPND) between the morphine and placebo sessions. (A) BPND maps averaged across all participants, coregistered to a common template for the morphine and (B) placebo infusion. (C) Statistical significance (t-score) map show a significant decrease in [11C]-raclopride BPnd in a large cluster encompassing the Putamen, Caudate and GP in response to morphine compared to placebo infusion (t = 3.5; p(FEW) = 0.005). (D) Four striatal regions of interest. (E) ΔBPnd for [11C]-raclopride between placebo and morphine sessions in four striatal regions of interest. Data are least square means (±s.e.m.). Sample size: 10 healthy, non-smoking, right-handed men. FWE, family-wise error. Error bars are s.e.m.