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The 41 amino acid peptide, corticotropin-releasing factor (CRF), isolated from ovine hypothalami has been shown to have sequence homologies with two other peptides, sauvagine (SA) and urotensin I (UT). All 3 of these peptides share some common biological properties in their ability to stimulate the release of ACTH from pituitary cells and cause vasodilation in defined vascular beds. CRF administered into the cerebral ventricles (i.c.v.) has previously been shown to have the additional property of being able to elicit behavior in the rat which has elements resembling the behavioral response to the stress of environmental novelty. The structurally related peptides SA and UT are shown here to have behavioral effects similar to those of CRF. When administered in doses of 0.5-2.0 micrograms i.c.v. 60 min prior to testing in a novel open-field environment, all 3 peptides cause a decrease in the amount of food consumed in the open field and a decrease in the mean amount eaten per approach to the food pedestal. They also decrease rearing and increase grooming. In addition, the 3 peptides caused the occurrence of a 'ballistic tail' phenomenon and a high frequency tremor in the forelimbs of several animals. The order of potency of the peptides in producing these effects was SA greater than or equal to CRF greater than UT. This order of potency differs from that previously reported for effects on vasodilation or on release of pituitary ACTH. The free acid C-terminus deaminated form of CRF (CRF-OH) failed to produce the profile of effects seen with the other peptides.

The ganglionic blocking agents, chlorisondamine (CL) and hexamethonium (HEX) were used to examine the role of altered autonomic function in the behavioral response to i.c.v.-administered corticotropin-releasing factor (CRF). Animals were tested in either a novel modified open field or in their home cages. CRF-induced alterations in locomotion, grooming and eating were assessed in both environments in the presence or absence of CL or HEX. In the home cage the ability of CRF to increase grooming was attenuated by pretreatment with either CL or HEX. In the modified open field only HEX significantly suppressed grooming. In the familiar environment CRF-induced increases in locomotion were significantly inhibited by CL. However, in a novel environment, where CRF suppresses locomotion, CL was inactive. The competitive ganglionic nicotinic blocking agent, HEX, on the other hand, inhibited both the increased locomotion produced by CRF in the home cage and also the decreased locomotion induced by CRF in the modified open field. CRF suppression of food consumption was attenuated by CL. These results indicate that while centrally-mediated activation of the sympathetic nervous system cannot account for the full magnitude of the behavioral effects of i.c.v. CRF, such activation may play a part in both the locomotor activating components of the CRF response seen in the familiar environment as well as the suppressive effects seen in the novel environment.