Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice.
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.
Ploj
K
K
Department of Pharmaceutical Biosciences, Division of Pharmacology, Uppsala University, Uppsala, Sweden.
Roman
E
E
Gustavsson
L
L
Nylander
I
I
D000428:Alcohol Drinking / Q000009:adverse effects; D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D004334:Drug Administration Schedule; D004399:Dynorphins / Q000187:drug effects* / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D004745:Enkephalins / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008811:Mice, Inbred DBA / Q000378:metabolism; D018847:Opioid Peptides / Q000187:drug effects* / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012646:Self Administration / Q000009:adverse effects; D000097629:Nociceptin
D004399:Dynorphins; D004723:Endorphins; D004744:Enkephalin, Methionine; D004745:Enkephalins; D000431:Ethanol; D018847:Opioid Peptides; D000097629:Nociceptin; C027511:enkephalin-Met, Arg(6)-Phe(7)-; C036200:rimorphin