Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice

Brain Res Bull. 2000 Sep 15;53(2):219-26. doi: 10.1016/s0361-9230(00)00328-2.


In order to investigate the involvement of the opioid and nociceptin/orphanin FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid peptides dynorphin B (DYNB) and Met-enkephalin-Arg(6) Phe(7) (MEAP) were examined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were compared in the brain and the pituitary gland with basal levels in the alcohol-avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-administration on peptides were studied in the C57BL/6J mice. Compared to the DBA/2J mice, C57BL/6J mice had low immunoreactive (ir) levels of DYNB and MEAP in the nucleus accumbens, the hippocampus, and the substantia nigra, low ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cortex. Higher ir-DYNB levels in the pituitary gland and in the periaqueductal gray (PAG) and higher ir-N/OFQ levels in the frontal cortex and in the hippocampus were detected in C57BL/6J mice compared to the DBA/2J mice. After 4 weeks of voluntary alcohol consumption, only minor changes in steady-state peptide levels were identified. However, 5 days after the alcohol-drinking period, lower levels of all peptides were detected in the ventral tegmental area and ir-DYNB levels were also lower in the amygdala and in the substantia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the PAG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the amygdala and substantia nigra as compared to control C57BL/6J mice. This study demonstrates strain differences between C57BL/6J mice and DBA/2J mice that could contribute to divergent drug-taking behaviour, and it also demonstrates time- and structure-specific changes in neuropeptide levels after alcohol self-administration in the C57BL/6J mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol-Induced Disorders, Nervous System / metabolism*
  • Alcohol-Induced Disorders, Nervous System / physiopathology
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Chemistry / physiology*
  • Drug Administration Schedule
  • Dynorphins / drug effects*
  • Dynorphins / metabolism
  • Endorphins / metabolism
  • Enkephalin, Methionine / analogs & derivatives*
  • Enkephalin, Methionine / metabolism
  • Enkephalins / drug effects*
  • Enkephalins / metabolism
  • Ethanol / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL / metabolism
  • Mice, Inbred DBA / metabolism
  • Opioid Peptides / drug effects*
  • Opioid Peptides / metabolism
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism
  • Self Administration / adverse effects


  • Endorphins
  • Enkephalins
  • Opioid Peptides
  • Ethanol
  • Enkephalin, Methionine
  • enkephalin-Met, Arg(6)-Phe(7)-
  • Dynorphins
  • nociceptin
  • rimorphin