The nitric oxide pathway is an important modulator of stress-induced fever in rats.

Psychological stress evokes a number of physiological responses, including a rise in body temperature (T(b)), which has been suggested to be the result of an elevation in the thermoregulatory set point, i.e., a fever. This response seems to share similar mechanisms with infectious fever. A growing number of studies have provided evidence that nitric oxide (NO) has a modulatory role in infectious fever, but no report exists about the participation of NO in stress fever. Thus, the present study aimed to verify the hypothesis that NO modulates stress fever by using restraint stress as a model. To this end, we tested the effects of the non-specific NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or its inactive enantiomer N(G)-nitro-D-arginine methyl ester (D-NAME) on colonic T(b) of restrained or unrestrained rats. A rapid increase in T(b) was observed when animals were submitted to restraint. Intravenous (i.v.) injection of L-NAME at a dose (10 mg/kg) that caused no change in T(b) when administered alone significantly attenuated the elevation in T(b) elicited by stress, indicating that the NO pathway may mediate stress fever. Moreover, intracerebroventricular (i.c.v.) L-NAME (250 microg/microl) caused a rise in T(b) of euthermic animals and enhanced stress fever, supporting that NO in the central nervous system (CNS) leads to a reduction in T(b) and, therefore, this is unlikely to be the site where NO may mediate stress fever. Taken together, these data indicate that the NO pathway plays an important role in modulating restraint stress-induced fever in rats.