Behavioral and neuroanatomical sequelae of prenatal naloxone administration in the rat

Pregnant Long-Evans hooded rats were dosed subcutaneously with 1 or 5 mg/kg/day naloxone hydrochloride, or an equal volume of vehicle, from gestational Day 4 (GD4) through GD19. Offspring were assessed for development of righting reflex, negative geotaxis, and open field activity, and for acquisition of a Warden maze; offspring sacrificed at postnatal Day (PND) 21 were assessed for several parameters of cerebellar, hippocampal, and motor cortical morphology. Five mg/kg/day naloxone accelerated development of negative geotaxis and righting reflex, while 1 mg/kg/day naloxone tended to slow development. Low dose females had significantly more errors than controls on the first day of maze learning. The high dose group had a significantly higher concentration of granule cells in the curvature of the dentate gyrus than controls; other neuroanatomical measures were unaffected by dosing. These findings confirm and extend previous work indicating that prenatal exposure to naloxone may alter neurobehavioral development in the rat.