Self administration of oxycodone by adolescent and adult mice affects striatal neurotransmitter receptor gene expression.
Illicit use of prescription opioid analgesics (e.g., oxycodone) in adolescence is a pressing public health issue. Our goal was to determine whether oxycodone self administration differentially affects striatal neurotransmitter receptor gene expression in the dorsal striatum of adolescent compared to adult C57BL/6J mice. Groups of adolescent mice (4 weeks old, n=12) and of adult mice (11 weeks old, n=11) underwent surgery during which a catheter was implanted into their jugular veins. After recovering from surgery, mice self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or served as yoked saline controls. Mice were sacrificed within 1h after the last self-administration session and the dorsal striatum was isolated for mRNA analysis. Gene expression was analyzed with real time PCR using a commercially available neurotransmitter receptor PCR array containing 84 genes. We found that adolescent mice self administered less oxycodone than adult mice over the 14 days. Monoamine oxidase A (Maoa) and neuropeptide Y receptor 5 mRNA levels were lower in adolescent mice than in adult mice without oxycodone exposure. Oxycodone self administration increased Maoa mRNA levels compared to controls in both age groups. There was a positive correlation of the amount of oxycodone self administered in the last session or across 14 sessions with Maoa mRNA levels. Gastrin-releasing peptide receptor mRNA showed a significant Drug × Age interaction, with point-wise significance. More genes in the dorsal striatum of adolescents (19) changed in response to oxycodone self administration compared to controls than in adult (4) mice. Overall, this study demonstrates that repeated oxycodone self administration alters neurotransmitter receptors gene expression in the dorsal striatum of adolescent and adult mice.
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
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B
Mayer-Blackwell
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
S D
SD
Schlussman
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
E R
ER
Butelman
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
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A
Ho
Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
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J
Ott
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
M J
MJ
Kreek
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. Electronic address: zhangyo@rockefeller.edu.
Y
Y
Zhang
D000367:Age Factors; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D058999:Drug-Seeking Behavior / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000378:metabolism; D010098:Oxycodone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012646:Self Administration
D009294:Narcotics; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; C100568:neuropeptide Y5 receptor; D010098:Oxycodone; D008995:Monoamine Oxidase
ANOVA; GRP; Grpr; MOP-r; Maoa; Npy5r; adolescent; adult; analysis of variance; dorsal striatum; gastrin-releasing peptide; gastrin-releasing peptide receptor; monoamine oxidase A; mu opioid receptors; neuropeptide Y receptor 5; neurotransmitter receptor gene expression; oxycodone; self administration