Adult behavior and adrenocortical function following neonatal morphine treatment in rats

Abstract

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.