Behavioral and developmental changes associated with prenatal opiate receptor blockade

Abstract

Pregnant Long-Evans hooded rats were dosed with 1, 5, or 10 mg/kg per day naloxone from gestational day 7 (GD7) through GD20. The control groups included both uninjected animals and injected animals pairfed to the 10-mg dose animals. At birth, all litters were culled to four males and four females, and fostered to undosed surrogate dams. Prenatal naloxone exposure produced changes in body weight development, pain sensitivity, and motor behavior in the offspring. Five and 10 mg/kg naloxone increased adult body weights in females only, as did the pairfeeding condition. The 10 mg/kg naloxone altered pain sensitivity (in males only) as measured by the tail flick test. Animals in the 1 mg/kg dose condition habituated more rapidly than uninjected (UN) subjects in the open field, and showed less activity than UNs as they matured. Bar pressing rates were reduced in the 10 mg/kg dose males in a visual discrimination task, while 10 mg/kg males and females showed reduced bar pressing rates on differential reinforcement of low rates of responding (DRL). These findings confirm that prenatal exposure to naloxone alters some aspects of neurobehavioral development in the rat, and are consistent with the hypothesis that 1 mg/kg prenatally may increase opiate function in offspring, while 10 mg/kg prenatally may decrease opiate functioning in the offspring.