Withdrawal-like symptoms in young and adult rats maternally exposed to methadone.

Rats of 30, 45, 60 and 120 days of age, maternally exposed to methadone (5 mg/kg daily) during gestation and/or lactation, were evaluated on a variety of behavioral and physiological parameters related to drug withdrawal. Animals were tested before and after an acute injection of naloxone (10 mg/kg). Prior to naloxone injection, methadone-exposed rats were subnormal in body temperature at 30 days of age, hypoalgesic at 45 days, and weighed less than controls at 60 days. Additionally, and in contrast to control rats, methadone-exposed animals at most ages displayed head shake and wet-dog shake behaviors. After naloxone administration, methadone-exposed rats exhibited an increase in the mean number of head and wet-dog shakes over pre-injection levels. Although control rats injected with naloxone also demonstrated head shakes (at all ages) and wet-dog shakes (at 45 days), these behavior were usually not of the magnitude as noted for methadone-exposed offspring receiving naloxone. Perturbations in body weight and hypothermia during development, along with head shake and wet-dog shake behaviors which were exacerbated following naloxone administration, suggest a protracted state of physical dependence/withdrawal and/or permanent damage as a result of perinatal exposure to methadone.