In Utero Cocaine Exposure and Persistent Changes in Cognition and Neurochemical Modulation

A growing body of evidence suggests that the cognitive changes produced by in utero cocaine exposure are subtle but functionally significant. The present studies were designed to investigate the influence of the timing and duration of exposure as well as the underlying neural mechanisms. In study one, rats were exposed to cocaine during either early or late in gestation or both ("full" exposure) and, in adulthood, tested on a series of extradimensional shift (EDS) tasks designed to tap attention and arousal. The pattern of changes during the early portion of the learning process indicated that for the cocaine-exposed animals, regardless of timing and duration of exposure, attention was captured by the most salient cues in the environment, which then affected attentional set formation and ease of shifting when task contingencies changed. In addition, both early- and "full"-exposed animals exhibited changes during the final learning phase indicative of impaired selective attention. In a second study, two doses of cocaine were explored: (1) 3.0 mg/kg cocaine once daily GD8-21 (1X COC) and (2) 3.0 mg/kg once/day GD8-16 and twice/day GD16-21 (2X COC). The pattern of findings suggested that the higher dose of cocaine significantly impaired transfer of learning involved in shifting attention, but only on EDS tasks in which the predictive stimuli were subtle relative to distractors. The lower cocaine dose impaired learning transfer both when distractors were salient and when they were subtle. Further, the lower dose of cocaine impaired selective attention. A final study examined correlations between density of ?2 receptors in prefrontal cortex (PFC) for the controls and 1X COC group. This study revealed that although density of alpha2 receptors in PFC did not differentiate the groups, nor did it predict performance in the control animals, this parameter did significantly predict performance of the COC rats. Specifically, those animals with low density of alpha2 receptors in PFC were significantly more impaired than those COC animals with high density of alpha2 receptors in PFC. These findings suggest that low alpha2 density in PFC may increase vulnerability to the lasting cognitive effects of prenatal cocaine exposure.NIH grants: R01DA13965 to Dr. Barbara Strupp (Cornell University, Department of Psychology) R01DA09160 to Dr. Charles Mactutus (University of South Carolina, Department of Psychology) K02DA014401 to Dr. Rosemarie Booze (University of South Carolina, Department of Psychology). NIEHS training grant in Environmental and Molecular Toxicology (5T32ES07052) at Cornell University (Dr. Andy Yen, Program Director and Dr. Stephen Bloom, Deputy Program Director)