TCAP-1 attenuates chronic stress in male rats, reducing corticosterone and improving behavior

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a core component of the stress response, contributing to anxiety, chronic stress, and neuropsychiatric disorders like major depressive disorder and posttraumatic stress disorder (PTSD). Current treatments often suffer from delayed efficacy and nonspecificity. Teneurin C-terminal Associated Peptide (TCAP)-1 is a naturally occurring neuropeptide known to regulate corticotropin-releasing factor (CRF)-mediated stress responses. While TCAP-1's effects on acute stress are established, its impact on chronic stress has remained unexplored, representing a critical gap in understanding its full therapeutic potential.

Researchers investigated the impact of TCAP-1 on chronic stress using a chronic unpredictable stress (CUS) model in male rats. The study administered TCAP-1 to a group of these stressed rats. For comparison, another group received CP-154,526, a nonpeptide CRF1 receptor antagonist, to evaluate its effects on the chronic stress-induced physiological and behavioral profile. Primary endpoints included plasma corticosterone levels, a physiological marker of stress, and open field center time, a behavioral measure reflecting anxiety-like states. Specific doses, routes, frequencies, or durations of administration were not detailed in the abstract.

Administration of TCAP-1 significantly attenuated the physiological and behavioral manifestations of chronic stress in male rats. Plasma corticosterone levels, a key indicator of HPA axis activity, were reduced by 56.4% in TCAP-1 treated animals. Behaviorally, TCAP-1 treatment led to a substantial increase in open field center time by 282.04%, indicating reduced anxiety-like behavior. This suggests a robust anxiolytic effect. In stark contrast, the nonpeptide CRF1 receptor antagonist, CP-154,526, demonstrated no significant effect on either the chronic stress-induced physiological or behavioral profile. This divergence highlights a critical difference in mechanism:

The lack of effect from the CRF1 receptor antagonist in this chronic model is consistent with the broader clinical failures of CRF1 receptor antagonists in human trials, underscoring TCAP-1's potential translational advantage via a distinct, likely upstream, mechanism of action.