The measurement of central nervous system peptides via chronic microdialysis as a function of social environment in the WHHL rabbit

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)



First Committee Member

Philip M. McCabe - Committee Chair


Our laboratory previously has shown that Watanabe Heritable Hyperlipidemic (WHHL) rabbits exposed to a stable social environment exhibited more affiliative social behavior and less aortic atherosclerosis compared to other social groups. Additional data suggests that central oxytocin (OXT) may be related to the expression of affiliative behavior and attenuation of peripheral stress responses. The purpose of this study is to examine central OXT responses and peripheral catecholamine and glucocorticoid responses during manipulations of the WHHL rabbit's social environment.Canulae implanted dorsal to the hypothalamic paraventricular nucleus (PVN) allowed chronic sampling via microdialysis. Rabbits were assigned to 1 of 3 social groups: an unstable group, with unfamiliar rabbits paired daily and pairings switched weekly; a stable group; with the same littermates remaining paired the entire study; and an individually caged group. Dialysates from the PVN and blood from the marginal ear vein were collected weekly from rabbits following 2-hours of exposure to their respective social condition. Dialysate was assayed for CNS OXT; plasma OXT, AVP, catecholamines and glucocorticoids also were measured.Mean changes (pre- post-pairing) in central OXT levels did not differ between the Stable group and the Unstable group following initial pairings. In contrast, hypothalamic OXT increased significantly in the Unstable group, but was relatively unchanged in the Stable group after 3 weeks of daily pairings. Because the Unstable group exhibited more agonistic behaviors and continued to exhibit hormonal stress responses on day 22, these results imply central OXT is a stress-sensitive neuropeptide. Interestingly, the Unstable group exhibited more atherosclerotic lesion area in the aortic arch than the other groups. Further analysis examined CNS OXT, peripheral OXT, AVP, catecholamines and glucocorticoids and their relation to specific social behaviors. CNS OXT was shown to correlate with corticosterone and to be inversely related to OXT and AVP found in the systemic blood supply. These data may further our knowledge of mechanisms underlying complex social behavior and its relationship to progression of atherosclerosis. Supported by NIH grants HL 36588 and HL 04726.


Biology, Neuroscience; Psychology, Physiological

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