Adult behavior and adrenocortical function following neonatal morphine treatment in rats

Adult behavioral and endocrine effects of neonatal administration of morphine (M) were studied in female rats injected s.c. with M on either days 3–12 (M₁) or days 12–21 (M₂). The dose given twice daily was increased to 8 mg/kg in group M₁ and to 16 mg/kg in group M₂. Compared to saline-treated controls, growth rates were temporarily suppressed (P<0.05) and body weights were reduced (P<0.05) util day 20 in M₁ and until day 64 in M₂ rats. The open-field test performed on days 29–31 failed to differentiate between neonatal treatment groups. On days 90–95 M₁ but not M₂ animals showed impaired learning of a conditioned emotional responses (CER). On day 40 all groups showed similar increased levels of plasma corticosterone 30 min following injection of naloxone (5 mg/kg). Compared to controls on day 156, both M₁ and M₂ rats showed diminished (P<0.05) analgesic responses (hot-plate test) to M (10 mg/kg). In response to M challenge (40 mg/kg) on day 170, all groups showed comparable acute increases in plasma corticosterone levels. These findings provide further evidence that early exposure to M results in growth retardation and protracted tolerance and that, depending on dose and time of exposure, neonatal M may result in impaired learning of CER in adulthood. These effects suggest that early morphine can produce long-lasting alterations of learned behavior without lasting impairment of pituitary-adrenal function.