Increased corticosterone pulse frequency during adjuvant-induced arthritisand its relationship to alterations in stress responsiveness

Frequent blood sampling from males rats was used to study hypothalamic-pitu itary-adrenal (HPA) axis activation during arthritis and its association wi th diminished responses to acute psychological stress. In control rats, cor ticosterone release occurred in a series of 13 +/- 1 pulses per 24 h. Induc tion of arthritis by Mycobacterium-adjuvant injection initially Increased t he rate of hormone release within each pulse and, by day 14 postinjection, when hind-paw inflammation was established, caused a marked increase in pul se frequency to 22 +/- 1 per 24 h leading directly to elevated circulating corticosterone levels. In both control and adjuvant-treated rats, there was a marked response to a 10-min noise stress when the stimulus coincided wit h a rising or interpulse phase of the endogenous corticosterone rhythm. How ever, when the noise stress coincided with a falling phase of this rhythm, the response was greatly diminished. Since corticosterone pulse frequency w as markedly increased and hence interpulse interval decreased by day 14, th ere was an increased probability of the noise stress occurring during the n onstress responsive failing phase of the corticosterone secretory cycle. As a result, the group mean response to noise stress was significantly smalle r in the arthritic than the controls (70.2 +/- 9.2 versus 107.8 +/- 13.0 ng /ml, respectively). In contrast to the differential response to noise stres s, all rats showed similar responses to the acute immunological challenge w ith i.v. lipopolysaccharide. Thus, altered basal pulse frequency Is a major factor influencing HPA activation during acute psychological stress.