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Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake
Published on: September 21, 2017
Assessing the contribution of opioid- and dopamine-related genetic polymorphisms to the abuse liability of oxycodone
Jermaine D Jones1, Mudassir Mumtaz2, Jeanne M Manubay1
1Division on Substance Use Disorders, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, 1051 Riverside Drive, New York, NY 10032, USA.
Background:
Attempts to identify opioid users at increased risk of escalating to opioid use disorder have had limited success. Data from a variety of sources suggest that genetic variation may mediate the subjective response to opioid drugs, and therefore contribute to their abuse potential. The goal of the current study was to observe the relationship between select genetic polymorphisms and the subjective effects of oxycodone under controlled clinical laboratory conditions.
Methods:
Non-dependent, volunteers with some history of prescription opioid exposure (N = 36) provided a blood sample for analyses of variations in the genes that encode for the μ-, κ- and δ-opioid receptors, and the dopamine metabolizing enzyme, catechol-O-methyltransferase (COMT). Participants then completed a single laboratory test session to evaluate the subjective and analgesic effects of oral oxycodone (0, 10, and 20 mg, cumulative dose = 30 mg).
Results:
Oxycodone produced typical μ-opioid receptor agonist effects, such as miosis, and decreased pain perception. Oxycodone also produced dose-dependent increases in positive subjective responses such as: drug "Liking" and "Good Effect." Genetic variants in the μ- (rs6848893) and δ-opioid receptor (rs581111) influenced the responses to oxycodone administration. Additionally, self-reported "Stimulated" effects of oxycodone varied significantly as a function of COMT rs4680 genotype.
Discussion:
The current study shows that the euphoric and stimulating effects of oxycodone can vary as a function of genetic variation. Though the relationship between the stimulating effects of opioids and their abuse liability is not well established, we know that the ability of opioids to provide intense feelings of pleasure is a significant motivator for continued use. If replicated, specific genetic variants may be useful in predicting who is at increased risk of developing maladaptive patterns of use following medical exposure to opioid analgesics.
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