James Schluger

Publications (2)17.67 Total impact

• Article: Hypothalamic-pituitary-adrenocortical (HPA) axis response and biotransformation of oral naltrexone: preliminary examination of relationship to family history of alcoholism.

  Andrea C King, James Schluger, Mithat Gunduz, Lisa Borg, Guillaume Perret, Ann Ho, Mary Jeanne Kreek
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  ABSTRACT: We examined HPA axis response to 50 mg oral naltrexone compared with placebo in 17 healthy male and female nonalcoholic subjects, approximately half of whom had a positive family history of alcoholism (FH+) and half of whom who did not (FH-). Mood response and naltrexone biotransformation were also examined at various intervals. Subjects participated in two morning test sessions (50 mg naltrexone or identical placebo pill) after an overnight stay in the Rockefeller University GCRC. For the total sample, ACTH and cortisol significantly increased after naltrexone compared with placebo (p <.05). Secondary analyses showed the FH+ subgroup had a different pattern of response over time compared with the FH- subgroup, with heightened ACTH and cortisol, and decreased vigor ratings, during naltrexone (p <.05). The results demonstrate that orally administered naltrexone acutely disinhibits the HPA axis, and that individuals with an assumed greater biological vulnerability to addiction, by virtue of familial alcoholism, had altered regulation of the HPA axis in part under the control of the endogenous opioid system. 166 words.
  Neuropsychopharmacology 07/2002; 26(6):778-88. · 7.99 Impact Factor
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  Available from: pnas.org

  Article: Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: Possible implications for opiate addiction

  Cherie Bond, K. Steven LaForge, Mingting Tian, Dorothy Melia, Shengwen Zhang, Lisa Borg, Jianhua Gong, James Schluger, Judith A. Strong, Suzanne M. Leal, Jay A. Tischfield, Mary Jeanne Kreek, Lei Yu
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  ABSTRACT: Opioid drugs play important roles in the clinical management of pain, as well as in the development and treatment of drug abuse. The mu opioid receptor is the primary site of action for the most commonly used opioids, including morphine, heroin, fentanyl, and methadone. By sequencing DNA from 113 former heroin addicts in methadone maintenance and 39 individuals with no history of drug or alcohol abuse or dependence, we have identified five different single-nucleotide polymorphisms (SNPs) in the coding region of the mu opioid receptor gene. The most prevalent SNP is a nucleotide substitution at position 118 (A118G), predicting an amino acid change at a putative N-glycosylation site. This SNP displays an allelic frequency of approximately 10% in our study population. Significant differences in allele distribution were observed among ethnic groups studied. The variant receptor resulting from the A118G SNP did not show altered binding affinities for most opioid peptides and alkaloids tested. However, the A118G variant receptor binds β-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor. Furthermore, β-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels. These results show that SNPs in the mu opioid receptor gene can alter binding and signal transduction in the resulting receptor and may have implications for normal physiology, therapeutics, and vulnerability to develop or protection from diverse diseases including the addictive diseases.
  Proceedings of the National Academy of Sciences 08/1998; 95(16):9608-9613. · 9.68 Impact Factor