Article

Opioid Receptor Imaging with Positron Emission Tomography and [18F]Cyclofoxy in Long-Term, Methadone-Treated Former Heroin Addicts

National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Journal of Pharmacology and Experimental Therapeutics (Impact Factor: 3.97). 12/2000; 295(3):1070-6.
Source: PubMed

ABSTRACT

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 [(18)F]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 [(18)F]cyclofoxy binding. Specific binding of [(18)F]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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    • "physiological, behavioural or neurobiological) that are believed to be correlated with craving, such as, changes in brain function revealed by neuroimaging technologies (e.g. Goudriaan, De Ruiter, Van Den Brink, Oosterlaan, & Veltman, 2010; Kling, et al., 2000; Martin-Soelch, et al., 2001; Sell, et al., 1999). Cue-reactivity in the absence of an opportunity to consume the drug of addiction does not have the same salience as cue-reactivity when drug consumption is possible. "
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    • "Brain PET: development, past, and future T Jones and EA Rabiner tomography has also been used to characterize dose–occupancy relationship for opioid substitute medications, methadone, and buprenorphine. While buprenorphine can be shown to occupy m-opioid receptors using [ 11 C]carfentanil PET (Greenwald et al, 2003), even high levels of methadone show limited or no occupancy of opioid receptors when using the nonsubtype-selective ligand [ 11 C]diprenorphine (Kling et al, 2000; Melichar et al, 2005), which questions the mode of action of methadone treatment. Many of the effects of alcohol in the brain are mediated by stimulating the GABA-benzodiazepine receptor. "
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    • "Brain PET: development, past, and future T Jones and EA Rabiner tomography has also been used to characterize dose–occupancy relationship for opioid substitute medications, methadone, and buprenorphine. While buprenorphine can be shown to occupy m-opioid receptors using [ 11 C]carfentanil PET (Greenwald et al, 2003), even high levels of methadone show limited or no occupancy of opioid receptors when using the nonsubtype-selective ligand [ 11 C]diprenorphine (Kling et al, 2000; Melichar et al, 2005), which questions the mode of action of methadone treatment. Many of the effects of alcohol in the brain are mediated by stimulating the GABA-benzodiazepine receptor. "
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