Effect of chronic stress on behavior and cerebral oxidative metabolism in rats with high or low positive affect.

The 50 kHz ultrasonic vocalizations (USVs) in rats have been associated with positive affect and rewarding experience. We have previously reported that stable inter-individual differences exist in the expression of these USVs (chirps). We have examined the effect of four weeks of chronic variable stress on cerebral oxidative metabolism, and depression and anxiety related behavior in male and female high (HC) and low (LC) chirping rats. Significant differences in regional oxidative metabolic activity as measured by cytochrome c oxidase (COX) histochemistry were found between male and female rats: Females had lower oxidative metabolism in several brainstem areas such as dorsal and median raphe and pontine nucleus, some cortical areas, and reward-related forebrain regions such as striatum and nucleus accumbens, but higher oxidative metabolism in amygdala and related limbic regions. Chronic stress increased oxidative metabolism in several depression-related brain regions in male but not female LC-rats such as amygdala, hippocampus and anterior thalamus. No systematic behavioral effect of stress was evident in females. In LC males, stress elicited increased levels of 22-kHz USVs, earlier and more stable reduction of weight gain, persistently lower sucrose intake and preference, and higher levels of immobility in the forced swimming test. These behavioral changes, accompanied by increased oxidative metabolism in limbic brain regions, indicate greater vulnerability to stress of male LC-rats, and suggest that in males low inherent positive affectivity predisposes to anxiety and affective disorders.