Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice

Neuroscience. 2015 Jan 29;285:34-46. doi: 10.1016/j.neuroscience.2014.11.013. Epub 2014 Nov 14.

Abstract

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) 2h/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.

Keywords: adolescent; adult; gene expression; hippocampus; oxycodone self-administration; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / drug effects
  • Aging / metabolism
  • Animals
  • Cadherins / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cyclic AMP Response Element Modulator / metabolism
  • Gene Expression
  • Gene Expression Regulation, Developmental / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Narcotics / administration & dosage*
  • Opioid-Related Disorders / metabolism*
  • Oxycodone / administration & dosage*
  • Proto-Oncogene Proteins c-pim-1 / metabolism
  • RNA, Messenger / metabolism
  • Receptor, Metabotropic Glutamate 5 / metabolism
  • Receptors, AMPA / metabolism
  • Self Administration

Substances

  • Cadherins
  • Cdh2 protein, mouse
  • Crem protein, mouse
  • Grm5 protein, mouse
  • Narcotics
  • RNA, Messenger
  • Receptor, Metabotropic Glutamate 5
  • Receptors, AMPA
  • Cyclic AMP Response Element Modulator
  • Oxycodone
  • Pim1 protein, mouse
  • Proto-Oncogene Proteins c-pim-1
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Camk2g protein, mouse
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • glutamate receptor ionotropic, AMPA 2