Publication Date


Document Type


Committee Members

Michael Hennessy (Advisor), Larry Ream (Committee Member), Patricia Schiml (Committee Member)

Degree Name

Master of Science (MS)


Isolation of guinea pig pups in a novel environment first produces active behaviors such as vocalizing and movement; over time, these behaviors wane and pups show characteristic passive responses similar to those produced by increased proinflammatory activity. Further, isolation of pups on two consecutive days has recently been shown to enhance those passive responses on the second day. Endogenous proinflammatory activity is thought to mediate the enhancement (sensitization). An injection of corticotropin-releasing factor (CRF) has been shown to increase passive behavior, possibly by increasing proinflammatory activity. The present study further investigated the role of CRF on proinflammatory activity and behavior during separation. In Experiment 1, pups were subcutaneously injected with 10μg of CRF or saline vehicle and then placed in a novel environment for 3 hr. CRF-injected pups exhibited more passive behavior and increased expression of the proinflammatory cytokine tumor necrosis factor alpha in the paraventricular nucleus of the hypothalamus when compared to saline injected pups. CRF increased plasma cortisol levels confirming that CRF activated the hypothalamic-pituitary-adrenal axis. In Experiment 2, pups were injected with either 75μg d-Phe12-41(CRF12-41), a corticotropin releasing factor antagonist, or saline vehicle and separated for 3 hr on two consecutive days. CRF12-41 increased active behaviors on Day 1. Passive behavior during separation was minimally affected by administration of the antagonist. In addition, passive responses increased from Day 1 to Day 2 in both the CRF12-41 and saline groups. Together, these findings provide evidence that exogenous CRF increases passive behavior through a proinflammatory mechanism, but also raise questions about the role of endogenous CRF in the separation response.

Page Count


Department or Program

Department of Neuroscience, Cell Biology & Physiology

Year Degree Awarded


Included in

Anatomy Commons