The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress

Rachel Y. Chong, Lynn Marie Oswald, Xiaoju Yang, Magdalena Uhart, Ping I. Lin, Gary S Wand

Research output: Contribution to journalArticle

Abstract

A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase β-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamic-pituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n = 74) and/or the modified Trier Social Stress Test (TSST) (n = 86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (P <0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P = 0.046), but a lower cortisol response to the TSST (P = 0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.

Original languageEnglish (US)
Pages (from-to)204-211
Number of pages8
JournalNeuropsychopharmacology
Volume31
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

mu Opioid Receptor
Naloxone
Hydrocortisone
Exercise Test
Adrenocorticotropic Hormone
Alleles
Pituitary Hormone-Releasing Hormones
Endorphins
Corticotropin-Releasing Hormone
Psychological Stress
Opioid Analgesics
Healthy Volunteers
Genotype
Pharmacology
Exercise
Neurons

Keywords

  • Adrenocorticotropin
  • Cortisol
  • Naloxone
  • Opioid receptor
  • Polymorphism
  • Stress

ASJC Scopus subject areas

  • Pharmacology

Cite this

The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. / Chong, Rachel Y.; Oswald, Lynn Marie; Yang, Xiaoju; Uhart, Magdalena; Lin, Ping I.; Wand, Gary S.

In: Neuropsychopharmacology, Vol. 31, No. 1, 01.2006, p. 204-211.

Research output: Contribution to journalArticle

Chong, Rachel Y. ; Oswald, Lynn Marie ; Yang, Xiaoju ; Uhart, Magdalena ; Lin, Ping I. ; Wand, Gary S. / The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. In: Neuropsychopharmacology. 2006 ; Vol. 31, No. 1. pp. 204-211.
@article{6c783a83a6fc441d930eaa85b9d3194a,
title = "The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress",
abstract = "A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase β-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamic-pituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n = 74) and/or the modified Trier Social Stress Test (TSST) (n = 86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (P <0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P = 0.046), but a lower cortisol response to the TSST (P = 0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.",
keywords = "Adrenocorticotropin, Cortisol, Naloxone, Opioid receptor, Polymorphism, Stress",
author = "Chong, {Rachel Y.} and Oswald, {Lynn Marie} and Xiaoju Yang and Magdalena Uhart and Lin, {Ping I.} and Wand, {Gary S}",
year = "2006",
month = "1",
doi = "10.1038/sj.npp.1300856",
language = "English (US)",
volume = "31",
pages = "204--211",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress

AU - Chong, Rachel Y.

AU - Oswald, Lynn Marie

AU - Yang, Xiaoju

AU - Uhart, Magdalena

AU - Lin, Ping I.

AU - Wand, Gary S

PY - 2006/1

Y1 - 2006/1

N2 - A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase β-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamic-pituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n = 74) and/or the modified Trier Social Stress Test (TSST) (n = 86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (P <0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P = 0.046), but a lower cortisol response to the TSST (P = 0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.

AB - A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase β-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamic-pituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n = 74) and/or the modified Trier Social Stress Test (TSST) (n = 86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (P <0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P = 0.046), but a lower cortisol response to the TSST (P = 0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.

KW - Adrenocorticotropin

KW - Cortisol

KW - Naloxone

KW - Opioid receptor

KW - Polymorphism

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=32844465629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32844465629&partnerID=8YFLogxK

U2 - 10.1038/sj.npp.1300856

DO - 10.1038/sj.npp.1300856

M3 - Article

C2 - 16123758

AN - SCOPUS:32844465629

VL - 31

SP - 204

EP - 211

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 1

ER -