Effects of neonatal handling on nociceptin/orphanin FQ and opioid peptide levels in female rats.
Animals exposed to short periods of handling during the critical period of development, i.e., the first 21 days of life in rats, show attenuated neuroendocrine responses to stress in adult life. We have previously reported long-term changes in brain dynorphin (DYN) peptide levels in male Sprague-Dawley rats after neonatal handling. The purpose of this study was to investigate whether neonatal handling, 15-min individual separation from the mother during postnatal days 1-21, can induce long-term changes in DYNB, Met-enkephalin Arg(6)Phe(7) (MEAP) and nociceptin/orphanin FQ (N/OFQ) immunoreactive (ir) levels in female Sprague-Dawley rats. The peptides were measured in brain and pituitary gland 2 months after the handling procedure. The results reveal that handled (H) rats had increased ir levels of N/OFQ, DYNB and MEAP in the periaqueductal gray (PAG) as compared to nonhandled (NH) controls. Furthermore, H rats had decreased ir levels of DYNB in the frontal cortex and in the amygdala. In contrast to previous findings in male rats, DYNB levels were unaffected in areas related to the hypothalamo-pituitary-adrenal (HPA)-axis. The results indicate that a manipulation early in life can induce persistent neurochemical changes in the N/OFQ and opioid peptide system in female Sprague-Dawley rats.