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/orphan in FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid pe ptides dynorphin B (DYNB) and Met-enkephalin-Arg(6) Phe(7) (MEAP) were exam ined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were com pared in the brain and the pituitary gland with basal levels in the alcohol -avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-adm inistration 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 M EAP in the nucleus accumbens, the hippocampus, and the substantia nigra, lo w ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cort ex. 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 hipp ocampus 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 tegmenta l area and ir-DYNB levels were also lower in the amygdala and in the substa ntia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the P AG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the am ygdala and substantia nigra as compared to control C57BL/6J mice. This stud y demonstrates strain differences between C57BL/6J mice and DBA/2J mice tha t could contribute to divergent drug-taking behaviour, and it also demonstr ates time- and structure-specific changes in neuropeptide levels after alco hol self-administration in the C57BL/6J mice. (C) 2000 Elsevier Science Inc .