EFFECTS OF NEONATAL TREATMENT WITH TYR-MIF-1, MORPHICEPTIN, AND MORPHINE ON DEVELOPMENT, TAIL-FLICK, AND BLOOD-BRAIN-BARRIER TRANSPORT

Morphine and endogenous peptides can alter developmental processes, inducing changes that can endure into adulthood. Morphiceptin binds to mu opiate receptors and to non-opiate sites labeled by Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), an endogenous brain peptide known to modulate opiate effects. Morphine, morphiceptin, Tyr-MIF-1, morphine + Tyr-MIF-1, and morphiceptin + Tyr-MIF-1 (50 mug, s.c.) were given to rats during their first week of life. Animals given morphine alone or in combination with Tyr-MIF-1 had significantly lower body weights for the first 3 weeks of life and delayed eye opening on day 16. Rats given morphine had hypersensitive tail flick responses on day 9 while those given morphine + Tyr-MIF- 1 were hypersensitive on days 3, 8, and 9. Locomotor, passive avoidance, and rotorod behaviors were not altered by the neonatal treatments. Transport of [I-125]Tyr-MIF-1 out of the brain was tested on day 23 and found to be increased by neonatal morphine, an effect that was significantly potentiated by neonatal Tyr-MIF-1. The results indicate that neonatal administration of peptides and opiates can affect later peptide transport across the blood-brain barrier as well as selected developmental characteristics.