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Vol. 295, Issue 3, 1070-1076, December 2000
Laboratory of the Biology of Addictive Diseases, The Rockefeller
University, New York, New York (L.B., J.S., A.H., M.J.K.); Clinical
Center, PET Department (R.E.C., P.H., W.C.E.), National Institute of
Mental Health (M.A.K., A.Z.), and National Institute of Diabetes and
Digestive and Kidney Diseases (K.C.R.), National Institutes of Health,
Bethesda, Maryland; and National Institute on Drug Abuse, National
Institutes of Health, Baltimore, Maryland (J.A.M.)
Stabilized methadone-maintained former heroin addicts (MTPs)
treated with effective doses of methadone have markedly reduced drug
craving; reduction or elimination of heroin use; normalized stress-responsive hypothalamic-pituitary-adrenal, reproductive, and
gastrointestinal function; and marked improvement in immune function
and normal responses to pain, all of which are physiological indices
modulated in part by endogenous and exogenous opioids directed at the
mu and, in some cases, the kappa-opioid systems. This study was
performed to explore opioid receptor binding in MTPs. Fourteen normal,
healthy volunteers and 14 long-term MTPs in treatment for 2 to 27 years
and receiving 30 to 90 mg/day of methadone were studied with positron
emission tomography using tracer amounts of
[18F]cyclofoxy, an opioid antagonist that labels mu and
kappa opioid receptors. Imaging was performed in the morning, 22 h
after the last dose of methadone in patients, and concurrent plasma
levels of methadone were determined. Five brain regions of specific
interest for addiction and pain research (thalamus, amygdala, caudate, anterior cingulate cortex, and putamen) were among the six regions of
highest [18F]cyclofoxy binding. Specific binding of
[18F]cyclofoxy was lower by 19 to 32% in these regions
in MTPs compared with those in normal volunteers. The degree to which
specific binding was lower in caudate and putamen correlated with
methadone plasma levels (P < .01 and
P < .05, respectively), suggesting that these
lower levels of binding may be related to receptor occupancy with
methadone and that significant numbers of opioid receptors may be
available to function in their normal physiological roles.
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