Neurobehavioral effects of prenatal morphine exposure in adulthood

Abstract

Prenatal exposure to moderate doses of morphine during gestation days 11-18 induces long-term alterations in adult rats. Analyses of mu-opioid receptor density in brain regions that modulate reward and anxiety revealed increased receptor density in the nucleus accumbens and central amygdala but decreased receptor density in the basolateral amygdala of adult, prenatally morphine-exposed males but not females. Therefore, the aim of the present study was to determine whether there are changes in behaviors that are regulated by these brain regions.;Because morphine preferentially activates the mu-opioid receptors, it was hypothesized that the increased receptor density may enhance the sensitivity to the rewarding and anxiolytic effects of acute morphine. These studies were performed in adult offspring of control (non injected), saline-injected or morphine-injected dams. The conditioned place-preference, intravenous self-administration and extinction paradigms were used to determine morphine reward. The elevated plus-maze was used to assess the anxiolytic properties of morphine.;All males developed place-preference to morphine, demonstrating that morphine was rewarding at all doses; however, females did not develop place-preference at the lowest dose of morphine, which suggests that the lowest dose was not rewarding in females. During self administration prenatally saline- and morphine-exposed males consumed less morphine than controls at the higher doses. This suggests that prenatally saline- and morphine-exposed males require lower doses of morphine than controls to achieve maximal reward. During extinction prenatally saline- and morphine-exposed males made fewer lever presses than controls, which suggests that they are less likely than controls to continue drug-seeking behavior in the absence of drug reward.;Although the response in the elevated plus-maze suggested that prenatally morphine-exposed males were more sensitive than controls or prenatally saline-exposed males to the anxiolytic effects of low morphine doses, the response was not consistent. Further, acute morphine was anxiolytic in prenatally saline-exposed males at a dose that had no effect in controls. In summary, prenatal morphine exposure does not enhance the rewarding effects of acute morphine in adulthood. These data suggest that prenatal manipulation induces long-term neurobehavioral alterations in adulthood. Future experiments will determine whether these alterations are due to prenatal stress or altered maternal behaviors.