The long-term consequences of prenatal exposure to cocaine remains a major public health concern. The presence of cocaine during critical periods of brain development could result in permanent changes in animals are necessary to answer two basic questions: 1) Do alternations in neural development resulting from prenatal cocaine exposure produce permanent changes in the structure of the brain? and (2) Does exposure to cocaine alter the neural and behavioral effects of cocaine later in life? These questions will be addressed by a combination of anatomical and behavioral analyses. The studies proposed here will focus on regions of the basal ganglia and limbic system that are most affected by cocaine's stimulant and epileptogenic actions. The experiments in section I will determine whether alterations in the distribution and density of dopaminergic and serotonergic afferents to the stratum, nucleus accumbens, cortex, hippocampus and amygdala occurs in prenatally cocaine-treated rats. The second set of experiments will examine differences in the behavioral and neural response to cocaine later in life, as a function of prenatal cocaine exposure. First, the ability of prenatally cocaine-treated rats to tolerate cocaine in adulthood will be examined by assessing seizure incidence after exposure to acute high doses or chronic lower doses of cocaine. These experiments will provide a behavioral index for assessing a greater sensitivity to the toxic effects of cocaine as a result of prenatal exposure. Next, we will examine induction of the immediate- early gene c-fos after re-exposure to cocaine later in life. Cells exhibiting increases in the Fos protein in response to cocaine or cocaine-induced seizures will be mapped using immunocytochemical techniques, and compared to the distribution of Fos-immunoreactive cells in normal animals. Correlations between regional anatomical alterations and changes in sensitivity to cocaine-induced seizures will be sought. In addition, we will vary the dose and timing of cocaine administration during development, in order to determine the critical period for the changes observed. These studies will help determine how early exposure to cocaine alters brain development in ways that affect later functioning.
