Effects of chronic episodic hypoxia on monoamine metabolism and motor activity

Chronic episodic hypoxia produces a wide array of cardiovascular dysfunctions in rats, including increases in blood pressure, heart rate, and sympathetic nerve activity. The action of episodic hypoxia might be related to low oxygen itself (hypoxemia) and/or combined with low CO2 (hypocapnia) resulting from hyperventilation. It is unknown whether or not the cardiovascular abnormalities are related to alterations in the central nervous system (CNS) that may be manifested as neurotransmitter and/or behavioral changes. In this study, we investigated effects of episodic eucapnic and hypocapnic hypoxia on monoamine metabolism in both CNS and adrenal glands, and on motor behavioral activity. Thirty-five male rats were divided into 3 groups. Experimental rats were exposed 8 h daily to varying fractional concentrations of inspired oxygen (FiO2) and carbon dioxide (FiCO2) for 35 days. These consisted of brief exposures (3-6s) of episodic (twice every min) eucapnic (3.5% FiO2 and 10% FiCO2, n = 6) or hypocapnic (3.5% FiO2 and 0% FiCO2, n = 14) hypoxia, or room air (21% FiO2 and 0.03% FiCO2, n = 15). Norepinephrine, dopamine, serotonin, and their metabolites in the hypothalamus, hippocampus, and adrenal glands were measured by high-performance liquid chromatography (HPLC). Spontaneous behavioral activity was assessed for 30 min by automated activity monitors. Episodic hypocapnic hypoxia produced a decrease in dopamine turnover and eucapnic hypoxia increased norepinephrine levels in the hypothalamus. Animals exposed to hypocapnic hypoxia also exhibited a consistent increase in horizontal (walking) and vertical (rearing) activity, as well as in total activity time. From these results, it is concluded that episodic eucapnic and hypocapnic hypoxia may affect metabolism of different neurotransmitters in the CNS.