Christine Wagner, Psychology Professor, Receives National Institutes of Health Grant

Christine Wagner

Sponsor:     National Institutes of Health
Dates:         January 1, 2014 – December 31, 2014
Amount:     $187,529

Synthetic Progestin Exposure & Mesocortical Dopamine System Development

The administration of synthetic progestins to pregnant women for the prevention of premature delivery has increased dramatically in recent years. Despite this increase, very little is known about either the role of endogenous progesterone in normal neural development, nor the potential deleterious effects of synthetic progestins on the developing brain. Preliminary data from rodent models suggest that progestins may play a role in the development of frontal cortex and the mesocortical dopamine system, a neurochemical pathway implicated in Attention Deficit Hyperactivity Disorder (ADHD). The objective of this proposal is to examine the effects of normal progesterone receptor function and exposure to the synthetic progestin, 17 hydroxprogesterone caproate in cortical development and subsequent cognitive behaviors using a rodent model. Aim 1 will test the hypothesis that progestin and progesterone receptor actions influence dendritic morphology and the expression of dendritic and synaptic proteins within frontal cortex. Aim 2 will test the hypothesis that progestin activity alters the rate of cell death and cell survival of “pioneer” cells of cortical subplate. Aim 3 will test the hypothesis that progestin activity alters the development of the mesocortical dopaminergic system. Aim 4 will test the hypothesis that progestin activity during development alters memory, cognitive flexibility and impulsive behavior in adulthood, as a model for ADHD-like behaviors. Results from these animal studies would vastly increase our knowledge about a role of progesterone and its receptor in normal cortical development and about the potential effects of progestin exposure to generate specific hypotheses for future research regarding outcomes in children exposed in utero.