Primavera A Spagnolo1, Alane Kimes2, Melanie L Schwandt3, Ehsan Shokri-Kojori4, Shantalaxmi Thada5, Karran A Phillips2, Nancy Diazgranados3, Kenzie L Preston2, Peter Herscovitch5, Dardo Tomasi4, Vijay A Ramchandani6, Markus Heilig7. 1. Human Motor Control Section, National Institute on Neurological Disorders and Stroke, National Instutes of Health, Bethesda, Maryland. 2. Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland. 3. Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Instutes of Health, Bethesda, Maryland. 4. Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Instutes of Health, Bethesda, Maryland. 5. Positron Emission Tomography Department, Clinical Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland. 6. Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, National Instutes of Health, Bethesda, Maryland. Electronic address: vijayr@mail.nih.gov. 7. Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden. Electronic address: markus.heilig@liu.se.
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.
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.
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