title: Acute opioid administration induces hypothalamic-pituitary-adrenal activation and is mediated by genetic variation in interleukin (Il)1B.
abstract: There is a complex relationship between drug dependence and stress, with alcohol and other drugs of abuse both relieving stress and potentially inducing physiological stress responses in the user. Opioid drugs have been shown to modulate hypothalamic-pituitary-adrenal (HPA) activity in animal models and individual response to this modulation may play a role in continuation of drug use. Healthy young Caucasian adults were administered a single dose of immediate release oxycodone (20mg, n=30) or assigned to a control group (n=19) that was not administered the drug. At 0, 1, 2, 4 and 6h post-administration, blood and saliva samples were collected along with assessment of pupil diameter. The HPA response was determined by measurement of salivary cortisol through a commercially available enzyme-linked immunosorbent assay (ELISA). The results were compared to genotype at the -511 and -31 positions in the interleukin1B (IL1B) gene. No difference in cortisol production was initially observed between the two groups, however, when participants were separated based on their genotype for two single nucleotide polymorphisms in the promoter of the IL1B gene, which have been shown to occur at a higher frequency in opioid-dependent populations, individuals carrying the -511T and -31 C alleles (-511 C/T, -31 C/T or -511 T/T, -31 C/C) had a significantly (p<0.05) higher cortisol levels compared to individuals homozygous for the -511 C and -31T alleles. These results suggest that individuals carrying the -511T and -31 C alleles experience HPA activation in response to opioid administration and therefore may be less likely to undertake subsequent self-administration.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Stephanie G
authors.initials: SG
authors.lastname: Kershaw
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia. Electronic address: Chris.DellaVedova@unisa.edu.au.
authors.forename: Chris B
authors.initials: CB
authors.lastname: Della Vedova
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Irina
authors.initials: I
authors.lastname: Majumder
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ward
authors.affiliation: School of Nursing and Midwifery, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Farquharson
authors.affiliation: Drug and Alcohol Services South Australia, Adelaide, South Australia, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Williamson
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Jason M
authors.initials: JM
authors.lastname: White
mesh_terms: D000483:Alleles; D000701:Analgesics, Opioid / Q000494:pharmacology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D009293:Opioid-Related Disorders / Q000235:genetics; D010098:Oxycodone / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011680:Pupil / Q000187:drug effects; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; C508585:IL1B protein, human; D053583:Interleukin-1beta; D010098:Oxycodone; D006854:Hydrocortisone
keywords: Cortisol; IL1B SNP polymorphism; Interleukin-1β; Opioid dependence; Oxycodone