Abstract

The effects of acute and chronic nicotine (N) administration on fetal electrocorticogram (ECoG) were investigated with spectral analysis. Fetal lambs were instrumented surgically to permit unanesthetized ECoG monitoring and N administration. Acute exposure studies used 4-hr constant-rate infusions at 0.6, 3 or 10 mg/hr. Chronic exposure studies used continuous infusions at 1.2 mg/hr for 7 days. The fast Fourier transform and several derivative parameters were used to quantitate the fetal ECoG during both control records and N infusions. Four states were identified and quantitated in the control ECoG: high-voltage slow activity (State I); low-voltage, fast activity (State IV); and two transitional states of intermediate amplitude and frequency. Acute N infusions elicited changes in the incidence and degree of electrocortical activation that were biphasically dose-related. The 0.6-mg/hr infusion evoked electrocortical activation through an increase in the incidence of State IV. Higher infusion rates elicited progressively less electrocortical activation. The 3-mg/hr infusion affected marginal activation, through a reduction in the incidence of State I. The 10-mg/hr infusion elicited mixed activation and depression, as assessed by multiple parameter changes. Desensitization of several responses diminished the magnitude of depressive effect observed during the 3- and 10-mg/hr infusions. Chronic nicotine infusions elicited progressive augmentation of electrocortical activation, through increases in the incidence and frequencies of State IV. Tolerance to this activating response was not observed.