Figure 3: Effects of prenatal exposure to different opioids on stress-induced neuronal activation in the PVH and LC. (a) Offspring without restraint (No-RST). (b) Offspring with RST. (c) Offspring with RST plus CRF receptor antagonist (α-helical CRF9-41; 10 μg/3 μL, i.c.v.). Data were obtained from adult male rat offspring with prenatal exposure to Veh, Bu, Meth, or Mor. cFos-ir cells were used as an indicator for neuronal activation. Data in each group are the mean ± SEM from six rats. *, P < 0.05, compared with Veh; #, P < 0.05, compared with Bu; +, P < 0.05, compared with Meth. Note that RST induced less neuronal activation in offspring with prenatal exposure to Meth or Mor, compared with those with prenatal exposure to Bu or Veh. This neuronal activation was completely prevented by CRF receptor antagonist in all study groups with RST. CRF: Corticotropin-releasing factor, Veh: Vehicle, Bu: Buprenorphine, Meth: Methadone, Mor: Morphine, cFos-ir: cFos-immunoreactive, LC: Locus coeruleus, PVH: Paraventricular nucleus in the hypothalamus.