Lasting effects of adolescent nicotine exposure on the electroencephalogram, event related potentials, and locomotor activity in the rat

Abstract

Tobacco smoking initiated during adolescence is often associated with rapid onset of dependence and difficulty in maintaining abstinence. Animal models have demonstrated that adolescent nicotine exposure causes cell death and altered neurochemistry in the cortex and hippocampus; however, little is known about the neurophysiological consequences of adolescent nicotine exposure in the adult. The primary objective of this study was to assess the consequences of adolescent nicotine exposure on the adult electroencephalogram (EEG) and event-related potentials. Male Sprague–Dawley rats were administered nicotine (5.0 mg/kg per day) for 5 days between postnatal days 35 and 40 using transdermal nicotine patches. Following 6–7 weeks of nicotine withdrawal, EEG activity and event related potentials were assessed. Motor activity and sucrose preference were also examined during the nicotine withdrawal period. Additionally, a set of rats was exposed to multiple doses of nicotine for a single day to assess nicotine and cotinine blood levels. Transdermal nicotine produced nicotine (88±21.5 ng/ml) and cotinine (647.6±123.2 ng/ml) levels comparable to those previously reported. Reduced motor activity, decreased 1–4 Hz power in the cortical electroencephalogram, and increased cortical N1 amplitude were observed in nicotine-exposed rats compared to controls. These data demonstrate that transdermal nicotine patches provide an effective and non-invasive nicotine delivery system for the adolescent rat. The combined neurophysiological and locomotor activity changes observed in nicotine-exposed rats demonstrate that adolescent nicotine exposure has lasting neurobehavioral consequences. These changes may be indicative of a lasting ‘nicotine abstinence syndrome’ characterized by increased arousal, anxiety, or emotionality.