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The relationship between naloxone‐induced cortisol and delta opioid receptor availability in mesolimbic structures is disrupted in alcohol‐dependent subjects
Author(s) -
Wand Gary S.,
Weerts Elise M.,
Kuwabara Hiroto,
Wong Dean F.,
Xu Xiaoqiang,
McCaul Mary E.
Publication year - 2013
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2011.00430.x
Subject(s) - medicine , endocrinology , naltrindole , (+) naloxone , opioid , ventral striatum , opioid receptor , psychology , alcohol dependence , mesolimbic pathway , hypothalamus , putamen , striatum , chemistry , receptor , alcohol , ventral tegmental area , dopamine , biochemistry , dopaminergic
Hypothalamic‐pituitary‐adrenal (HPA) axis responses following naloxone administration have been assumed to provide a measure of opioid receptor activity. Employing positron emission tomography (PET) using the mu opioid receptor (MOR) selective ligand [ 11 C] carfentanil (CFN), we demonstrated that cortisol responses to naloxone administration were negatively correlated with MOR availability. In this study, we examined whether naloxone‐induced cortisol and adrenocorticotropin (ACTH) responses in 15 healthy control and 20 recently detoxified alcohol‐dependent subjects correlated with delta opioid receptor (DOR) availability in 15 brain regions using the DOR‐selective ligand [ 11 C] methyl‐naltrindole (MeNTL) and PET imaging. The day after the scan, cortisol responses to cumulative doses of naloxone were determined. Peak cortisol and ACTH levels and area under the cortisol and ACTH curve did not differ by group. There were negative relationships between cortisol area under curve to naloxone and [ 11 C] MeNTL‐binding potential (BP ND ) in the ventral striatum, anterior cingulate, fusiform cortices, temporal cortex, putamen and a trend in the hypothalamus of healthy control subjects. However, in alcohol‐dependent subjects, cortisol responses did not correlate with [ 11 C]MeNTL BP ND in any brain region. Plasma ACTH levels did not correlate with [ 11 C]MeNTL BP ND in either group. The study demonstrates that naloxone provides information about individual differences in DOR availability in several mesolimbic structures. The data also show that the HPA axis is intimately connected with mesolimbic stress pathways through opioidergic neurotransmission in healthy subjects but this relationship is disrupted during early abstinence in alcohol‐dependent subjects.