Nicotine withdrawal after chronic exposure in adulthood blunts the ventilatory response to hypoxia in rats

Abstract

Nicotine is one of the most addictive substances known, and it is estimated that 50.6 million US adults use nicotine in some form. It is well known that smoking, the most common form of nicotine exposure, alters lung structure and function. In contrast, the impact of chronic nicotine exposure during adulthood on neural structures involved in the control of breathing is largely unknown. In preliminary experiments in adult rats, we used plethysmography to study the effects of chronic nicotine exposure on the ventilatory response to hypoxia, which is a critical respiratory chemoreflex that enhances breathing and limits arterial O2 desaturation. Four weeks of chronic nicotine exposure through drinking water had no effect on the ventilatory response to a brief, 5‐ minute episode of hypoxia (10%) (Minute ventilation: One‐way ANOVA, Control vs Nicotine Exposure; P=0.6533). In contrast, nicotine exposed rats show a significantly blunted ventilatory response to hypoxia following 48 hours of nicotine withdrawal (Control vs Nicotine Withdrawal, P=0.0447). The reduced ventilatory response was due to a blunted increase in tidal volume (Amplitude: One‐way ANOVA, Control vs Nicotine Withdrawal; P=0.007), with a normal frequency response (Control vs Nicotine Withdrawal; P=0.2518. This has important clinical ramifications, as hypoxia is a commonly encountered medical complication, and withdrawal symptoms are often observed in hospitalized patients as it is common for them to abstain from smoking during periods of worsening health or in preparation for surgery.