The effects of corticotropin-releasing factor on the cortical EEG are reduced following adolescent nicotine exposure

Abstract

Although smoking is highly prevalent among adolescents, relatively little is known about the lasting neurobehavioral consequences associated with adolescent nicotine exposure. Prior studies from our laboratory suggest that adolescent nicotine exposure induces an anxiogenic profile in adult rats. Corticotropin-releasing factor (CRF) systems are important modulators of anxiety and response to stress. Since acute nicotine administration has been shown to stimulate central CRF activity, the purpose of this study was to examine the effects of adolescent nicotine exposure on CRFs modulation of the cortical and hippocampal EEG in adult rats. Male Sprague–Dawley rats were exposed to nicotine (5 mg/kg/day) between postnatal days 35–40 using transdermal nicotine patches. Six weeks after nicotine exposure ended, the effects of intracerebroventricular administration of CRF (0.01– 1.0 μg/5 μl ) on EEG activity in the cortex and hippocampus were assessed in nicotine-exposed rats and age-matched control rats. The overall effects CRF were consistent with previous reports. CRF decreased low to moderate frequency EEG activity (1–32 Hz) and increased high frequency EEG activity (32–50 Hz). However, in nicotine-exposed rats the effects of CRF on the frontal and parietal cortical EEG were blunted by 30–50% compared to control rats. A similar pattern of decreased response to CRF was not observed in the hippocampus. These blunted effects of CRF on the cortical EEG suggest that long-term changes in systems responsive to CRF result from adolescent nicotine exposure. Given the role of CRF systems in behavioral responses to stress and anxiety, these data suggest that adolescent nicotine exposure may produce long-term decreases in neurophysiological responses to stress.