We report here on the immunological and behavioral alterations induced by stimulation of the mesencephalic periaqueductal gray matter (PAG), a component of the brain aversive system. Male Wistar rats were implanted with stimulating electrodes in the caudal dorsolateral part of the PAG. After recovery, animals were screened for aversive behavior, characterized by running, jumping, vocalization or freezing reaction. Then, rats were subdivided to those which could control aversive stimulation (AS) by switch-off response (cAS group) and those which could not interrupt AS (uAS group). After sensitization with bovine serum albumin (BSA) in complete Freund's adjuvant, rats were stimulated 3 times/week for 40 days, each session lasting 30 min/rat. Immunological assessment included antibody production and hypersensitivity skin reactions to BSA 14 and 21 days after immunization. A behavioral profile of aversively stimulated animals was determined by a poststartle response, open field (OF) activity and two-way shuttle-box avoidance task. The results revealed elevated antibody production to BSA in cAS and lowered in uAS rats, compared to sham-stimulated and intact controls. Arthus and delayed hypersensitivity skin reactions increased in PAG-stimulated animals on day 14 but not on day 21 after immunization. Poststartle response was enhanced both in cAS and uAS rats. Along with immunopotentiation, administration of cAS produced hyperactivity in OF test and facilitation of the active avoidance learning, whereas uAS caused only moderate suppression of rearing in a novel OF environment. Physiological implications and possible mechanisms that may account for PAG-mediated immunobehavioral changes are outlined.

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