Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice
| Autor: | Jurg Ott, Michele Buonora, A.J. Brownstein, Ann Ho, Mary Jeanne Kreek, Keiichi Niikura, Yong Zhang, J. Correa da Rosa |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Narcotics CAMP-Responsive Element Modulator Aging Receptor Metabotropic Glutamate 5 Hippocampus Gene Expression Self Administration Pharmacology Article Cyclic AMP Response Element Modulator Proto-Oncogene Proteins c-pim-1 Neurotransmitter receptor Medicine Animals RNA Messenger Receptors AMPA education Mitogen-Activated Protein Kinase 1 education.field_of_study business.industry General Neuroscience Glutamate receptor Gene Expression Regulation Developmental Long-term potentiation Cadherins Opioid-Related Disorders Mice Inbred C57BL Metabotropic receptor Synaptic plasticity business Calcium-Calmodulin-Dependent Protein Kinase Type 2 Oxycodone medicine.drug |
| Zdroj: | Neuroscience. 285 |
| ISSN: | 1873-7544 |
| Popis: | Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available “synaptic plasticity” PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus of adolescent and adult mice. |
| Databáze: | OpenAIRE |
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