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Striatal Dopamine Release in Response to Morphine: A [C-11]Raclopride Positron Emission Tomography Study in Healthy Men
NINDS, MD 20892 USA.
NIDA, MD 20892 USA.
NIAAA, MD 20892 USA.
NIAAA, MD 20892 USA.
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2019 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 86, no 5, p. 356-364Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2019. Vol. 86, no 5, p. 356-364
Keywords [en]
[C-11]Raclopride; Dopamine; Morphine; Opioids; PET; Ventral striatum
National Category
Physiology
Identifiers
URN: urn:nbn:se:liu:diva-159851DOI: 10.1016/j.biopsych.2019.03.965ISI: 000480435400008PubMedID: 31097294OAI: oai:DiVA.org:liu-159851DiVA, id: diva2:1346297
Note

Funding Agencies|National Institute on Drug Abuse intramural research program; National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research Grant [Z1A-AA000466]

Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-08-27

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