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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 \u00b1 2.9% baseline vs. HU: 58 \u00b1 4.5% baseline) and reduced (rightward shift) operant responding for rewarding electrical brain stimulation (CC: 4.4 \u00b1 0.3 \u03bcA vs. 7.3 \u00b1 1.0 \u03bcA). Cardiac autonomic blockade revealed elevated sympathetic [CC: \u221254 \u00b1 14.1 change in (\u0394) beats\/min vs. HU: \u2212118 \u00b1 7.6 \u0394 beats\/min] and reduced parasympathetic (CC: 45 \u00b1 11.8 \u0394 beats\/min vs. HU: 8 \u00b1 7.3 \u0394 beats\/min) cardiac tone in HU rats. Heart rate variability was reduced (CC: 10 \u00b1 1.4 ms vs. HU: 7 \u00b1 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. 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