Behavioral effects of peripheral corticotropin-releasing factor during maternal separation may be mediated by proinflammatory activity.

When guinea pig pups are separated from their mothers in a novel environment, an initial period of active behavior (vocalizing, locomotor activity) wanes after an hour or so and is replaced by a second, passive stage characterized by a crouched stance, closed eyes, and extensive piloerection. If pups are given a peripheral injection of 7-14μg of corticotropin-releasing factor (CRF) prior to testing, the passive behaviors occur immediately upon separation. We found that intracerebroventricular infusion of 1-10μg of CRF did not increase passive behavior relative to vehicle infusion, but that peripheral injection of the anti-inflammatory cytokine, interleukin-10, attenuated the passive behavior induced by peripheral CRF injection. These results together with previous findings suggest that peripheral CRF administration affects behavior of separated guinea pig pups through a mechanism that involves peripheral proinflammatory activity. The possible role of endogenous peripheral CRF in the behavioral response of untreated pups during maternal separation is considered.