Abstract
Blockade of brain μ-opioid receptor (μ-OR) and δ-opioid receptor (δ-OR) was investigated in recently abstinent alcohol-dependent subjects (N=21) maintained on naltrexone. Subjects completed a 19-day inpatient protocol, which included alcohol abstinence followed by naltrexone treatment (50 mg) on days 15-19. Blood samples were collected after the first administration of naltrexone to evaluate serum levels of naltrexone and 6-β-naltrexol. Regional brain μ-OR binding potential (BP) and δ-OR Ki was measured using [11C]carfentanil (CAR) positron emission tomography (PET) and [11C]methyl naltrindole ([11C]MeNTI) PET, respectively, before (day 5) and during naltrexone treatment (day 18). Naltrexone inhibition of [11C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean+SD% inhibition=94.9+4.9%). Naltrexone only partially inhibited the [ 11C]MeNTI Ki and there was more variability across subjects (mean+SD% inhibition=21.1+14.49%). Peak serum levels of naltrexone were positively correlated with % inhibition of δ-OR Ki in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of μ-OR BP. Peak levels of 6-β-naltrexol were not significantly correlated with % inhibition of μ-OR BP or δ-OR K i. Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the μ-OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of δ-OR and greater variability in δ-OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone. Further investigations on the relationship between individual differences in δ-OR blockade by naltrexone and clinical outcomes should be explored.
Original language | English (US) |
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Pages (from-to) | 653-665 |
Number of pages | 13 |
Journal | Neuropsychopharmacology |
Volume | 33 |
Issue number | 3 |
DOIs | |
State | Published - Feb 2008 |
Keywords
- Alcoholism
- Dependence
- Naltrexone
- PET imaging
- δ-opioid receptors
- μ-opioid receptors
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health