Ontogenetic changes in ethanol's motivational properties: Involvement of the kapp

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Fetal alcohol exposure in humans is recognized as a likely contributor to alcohol abuse during adolescence and adulthood. Exposure to ethanol in laboratory rodents during the first two postnatal weeks is widely used as an experimental model of human fetal alcohol exposure, given its accepted value as a neurological model for the third trimester of human fetal development. Such early exposure has been shown to significantly increase ethanol intake later in life. The neural mechanisms susceptible to early ethanol exposure and responsible for the reported increased propensity for ethanol intake are yet to be investigated. The endogenous dynorphin/kappa opioid receptor system is of great interest due to its possible involvement in diminishing ethanol intake through modulation of its aversive properties. There is some experimental evidence, although still limited, that motivational properties of the dynorphin/kappa opioid receptor system change across ontogeny, with newborn and infant rats finding activation of kappa opioid receptors appetitive and adult rats demonstrating aversive responding. These findings, in turn, suggest ontogenetic differences in the kappa opioid receptor involvement in ethanol intake and reinforcement based, presumably, on ontogenetic changes in motivational properties of the dynorphin/ kappa opioid receptor system. The present proposal will test the hypothesis that the motivational properties of the kappa opioid system switch from appetitive to aversive during the 2nd postnatal week, with this switch being parallel to an ontogenetic increase in sensitivity to the aversive properties of ethanol. Exposure to ethanol early in life, especially during the period when the dynorphin/kappa opioid receptor system functions to mediate appetitive reinforcement, alters the aversive motivational properties of this system, with this alteration contributing to the propensity to consume large amounts of ethanol without experiencing its aversive consequences later in ontogeny. PUBLIC HEALTH RELEVANCE: Exposure to alcohol early in life is a major contributing factor to future use and abuse of the drug. The kappa/dynorphin opioid system seems to be critically involved in modulating the aversive properties of ethanol during adulthood. The function of this system may change as a result of early alcohol exposure. The proposed experiments will dissect the changes in the motivational properties of ethanol and the kappa/dynorphin system across the first two weeks of life. Furthermore, these studies will investigate possible effect of early ethanol exposure on the motivational properties of ethanol and kappa opioid system.