The Role of Altered Catecholaminergic Activity in the Attentional Dysfunction Induced by Lead Exposure or Prenatal Cocaine Exposure
Attentional dysfunction is associated with numerous genetic and environmental factors that disrupt brain development. Evidence implicates catecholaminergic systems in attentional processing, suggesting that alterations in catecholamine neurochemistry may underlie these attentional dysfunctions. The goal of the present experiments was to use a pharmacological challenge approach to examine underlying neural changes that relate to attentional dysfunctions induced by two developmental insults, lead (Pb) exposure and prenatal cocaine exposure, and to test the hypothesis that exposure-induced alterations in catecholaminergic systems contribute to these attentional deficits. In each experiment, adult rats were administered a visual attention task which assessed subjects' ability to monitor an unpredictable light cue and maintain performance when presented with olfactory distractors. In the first study, Pb-exposed subjects demonstrated significant impairments in accuracy relative to controls, providing evidence for Pb-induced attentional dysfunction. The alpha-2 adrenergic antagonist idazoxan improved accuracy, specifically in the most attentionally demanding conditions. However, this effect of idazoxan did not differ between Pb-exposed and control subjects, failing to support the hypothesis that the attentional dysfunction was due to alterations in noradrenergic systems. In the second study, prenatal cocaine-exposed subjects did not differ from controls in their response to idazoxan's effect on errors of commission, but were more sensitive to idazoxan's effects on errors of omission and nontrials. The pattern of effects suggested that the differential treatment response to idazoxan resulted from prenatal cocaine-induced alterations in norepinephrine-modulated dopamine release, reflecting lasting changes in dopaminergic and/or noradrenergic systems underlying attention. The final study was designed to assess whether cocaine exposed and control subjects differ in sensitivity to attentional effects of the D1 dopamine agonist SKF81297. Prenatal cocaine-exposed subjects were more sensitive to the impairing effects of SKF81297 on errors of omission, providing specific evidence that prenatal cocaine exposure produces lasting changes in dopaminergic systems mediating attention. In conclusion, environmental Pb exposure impairs attention; however, these impairments do not appear to reflect alterations in noradrenergic function, suggesting the involvement of other neurochemical systems. In contrast, prenatal cocaine-induced attentional impairments appear to be related to lasting changes in dopaminergic systems underlying attention, suggesting possible targets for pharmacotherapeutic intervention in affected children.
attention; dopamine; norepinephrine; prenatal cocaine exposure; lead exposure; catecholamines
dissertation or thesis