Abuse of substances such as heroin and methadone during pregnancy is widespread and there is concern about the placental transfer of such drugs and the possible effects on the developing fetus. There has been much basic research on the effects of prenatal opiate exposure on both behavior as well as neural function. However, much of this research has focused on the early neonatal period or adulthood. The effects on the juvenile animal have not been as well investigated. It is possible that prenatal opiate exposure may have subtle neural and behavioral consequences that are not apparent in the neonatal period or that emerge later. One system that is most likely affected by prenatal exposure to opiates are the endogenous opioids, which develop prenatally. Opioids mediate many behaviors in both the human and the rat. One such behavior is play, a social behavior that is exhibited by juveniles of most mammalian species. Acute administration (in the juvenile period) of opiate agonists increase play, whereas acute administration of opiate antagonists decrease play. When exposure to opiates occur prenatally, differences in play are also observed, depending on the method of prenatal administration. Intermittent administration of an opiate agonist (i.e. morphine) prenatally increases play, but continuous prenatal administration decreases play. Intermittent prenatal administration produces fluctuating (blood plasma) opiate levels, causing the dam and the fetuses to experience both the effects of the opiate and short term withdrawal from the opiate. Conversely, chronic administration produces relatively constant opiate levels. Thus, different methods of prenatal administration could have different neural consequences, which would subsequently produce the changes in play behavior.
The specific aims of this proposal are to examine the effects of different methods of prenatal opiate administration over the time course of gestation on play behavior and the endogenous opioids.
These aims will be accomplished through both behavioral and molecular techniques. Understanding the neural mechanisms underlying the behavioral changes will provide a model from which to examine the consequences of maternal drug use in humans.
