Teneurin C-terminal associated peptide (TCAP)-1 attenuates corticotropin-releasing factor (CRF)-induced c-Fos expression in the limbic system and modulates anxiety behavior in male Wistar rats

The teneurin C-terminal associated peptides (TCAPs) are a novel family of four endogenous peptides that have previously shown bioactive properties both in vitro and in vivo. Previously we have shown that repeated intracerebral injections of synthetic TCAP-1 modulate anxiety-like behaviors in three tests of anxiety, although the neural substrates responsible for these effects were previously unknown. In the current study, we examined both c-Fos induction and behavioral responses in the elevated plus maze and open field tests after a single intracerebroventricular dose of TCAP-1 followed by an intracerebroventricular injection of CRF in male Wistar rats. The results indicate that TCAP-1 injection attenuated the CRF-induced increase in c-Fos expression in the limbic system and many of the areas associated with the behavioral responses to stress, including the hippocampus, central and basolateral nuclei of the amygdala, medial prefrontal cortex, and dorsal raphe nucleus. Other areas, such as the paraventricular nucleus of the hypothalamus, bed nucleus of the stria terminalis, medial nucleus of the amygdala, and locus coeruleus, displayed CRF-induced c-Fos levels that were unaffected by TCAP-1. Furthermore, TCAP-1 administration increased stretched-attend postures, a type of risk-assessment behavior, on the elevated plus maze. These results indicate that TCAP-1 may play a potential role in the regulation of stress by blocking CRF-mediated activity in specific stress-sensitive areas of the brain.