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Exendin-4 increases absence-like seizures and anxiety-depression-like behaviors in WAG/Rij rats

A controlled study (PMID: 7777652) found that DSIP did not significantly affect CRH- or meal-induced ACTH and cortisol secretionindicating DSIP does not measurably blunt the human cortisol response, contrary to stress-protective effects suggested by some animal studies

Answer: GLP-1 medications such as semaglutide and tirzepatide act on the GLP-1 pathway, while cagrilintide acts on the separate amylin pathway, which is why the two are additive rather than redundant when used together

However, this review also critically evaluates alternative explanations for the translational gap, including limited central nervous system penetration, insufficient pharmacodynamic target engagement, a mismatch between the drugs metabolic mechanisms and the amyloid-driven pathology of established AD, and the inherent limitations of preclinical models

Rabbits were anesthetized for these measurements, using the same protocol as for wound creation

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