Subsequent anxiety-related behavior in rats exposed to low-dose methadone during gestation, lactation or both periods consecutively

Abstract

In order to assess the long-term behavioral consequences of exposing rats to methadone during gestation, lactation or both periods consecutively, pregnant Wistar dams were provided with drinking water containing approximately 2.39mg/kg/day methadone. Soon after birth, litters of offspring were assigned to methadone-naïve foster mothers. Half of these foster mothers were then provided with drinking water containing methadone (approximately 2.86mg/kg/day), while the other half received unadulterated water. Maternal weight gain, pregnancy duration, litter sizes, sex ratios and average pup weights were recorded. Following weaning on postnatal day (PND) 28, individual rats were weighed and inspected for physical abnormalities and stress reactions at PND20, 60 and 120. At these same ages, observations were also made of the rats' behavior in an emergence apparatus, and an open field. Apart from a smaller number of full-term pregnancies, there were no effects of any type of methadone treatment on physical measurements recorded at any age. Nor were there any behavioral effects of gestational methadone experienced on its own. However, methadone experienced during lactation (without gestational exposure) decreased emergence speed at PND30, and for all testing ages combined, increased open-field ambulation (males only), walking, rearing and occupancy of the center of the apparatus. Exposure to methadone during both gestation and lactation decreased emergence latencies at PND30 and, for all ages combined, decreased ambulation (males only), center occupancy and defecation. The subsequent behavioral effects of methadone were largely confined to lactational exposure and, when combined with gestational exposure, suggested increased anxiety.