Adverse social environments are an important etiological factor in the onset of mood disorders. The aim of this study was to evaluate the occurrence of behavioral and physiological signs of a depression-like state in rats exposed to social defeat and isolation. Adult male rats were implanted with radiotransmitters for ECG, temperature (T) and activity (Act) recordings. Treated rats (SDI, n=22) were exposed to a single defeat episode followed by 4-week social isolation, while controls (CTR, n=22) were simply introduced to an unfamiliar cage and went back to pair housing with a female. During isolation, cardiac sympathovagal balance in the open field test and hypothalamic-pituitary-adrenal axis (HPAA) reactivity to a dexamethasone suppression test were assessed. Before and after defeat, hedonic behavior (preference for a sucrose solution) and around-the-clock heart rate (HR), T, and Act were recorded. HPAA function was heightened in SDIs as compared to CTRs 10 days after defeat, as shown by significantly higher plasma corticosterone levels. SDIs also showed a significant reduction of sucrose solution consumption 3 weeks after defeat, and a reduction in the amplitude of HR and Act daily rhythms. Unlike CTR rats, SDIs did not show habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) upon re-exposure to open field test. In conclusion, defeat and isolation seem to represent a valid experimental paradigm for mimicking depression in the laboratory rat.