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Departments of 1Psychology, 2Integrative Physiology, and 3Pharmacology, and 4Cardiovascular Center, University of Iowa, Iowa City, Iowa
Submitted 16 April 2008 ; accepted in final form 10 July 2008
The hindlimb-unloaded (HU) rat model elicits cardiovascular deconditioning and simulates the physiological adaptations to microgravity or prolonged bed rest in humans. Although psychological deficits have been documented following bed rest and spaceflight in humans, few studies have explored the psychological effects of cardiovascular deconditioning in animal models. Given the bidirectional link established between cardiac autonomic imbalance and psychological depression in both humans and in animal models, we hypothesized that hindlimb unloading would elicit an alteration in sympathovagal tone and behavioral indexes of psychological depression. Male, Sprague-Dawley rats confined to 14 days of HU displayed anhedonia (a core feature of human depression) compared with casted control (CC) animals evidenced by reduced sucrose preference (CC: 81 ± 2.9% baseline vs. HU: 58 ± 4.5% baseline) and reduced (rightward shift) operant responding for rewarding electrical brain stimulation (CC: 4.4 ± 0.3 µA vs. 7.3 ± 1.0 µA). Cardiac autonomic blockade revealed elevated sympathetic [CC: –54 ± 14.1 change in (
) beats/min vs. HU: –118 ± 7.6
beats/min] and reduced parasympathetic (CC: 45 ± 11.8
beats/min vs. HU: 8 ± 7.3
beats/min) cardiac tone in HU rats. Heart rate variability was reduced (CC: 10 ± 1.4 ms vs. HU: 7 ± 0.7 ms), and spectral analysis of blood pressure indicated loss of total, low-, and high-frequency power, consistent with attenuated baroreflex function. These data indicate that cardiovascular deconditioning results in sympathovagal imbalance and behavioral signs consistent with psychological depression. These findings further elucidate the pathophysiological link between cardiovascular diseases and affective disorders.
hindlimb suspension; microgravity; deconditioning; depression; sympathetic; parasympathetic
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