Salivary Chromogranin A (CgA) Response to the Noradrenaline Transporter Blocker Atomoxetine in Dogs

Abstract

Simple Summary Cortisol in peripheral samples (e.g., blood, saliva or hair) is commonly used for the assessment of stress in dogs. It primarily reflects the hypothalamus–pituitary–adrenal (HPA) axis responses and serves as a marker to indicate the rapid response via the sympathetic adrenomedullar system (SAM), which has not yet been well studied in dogs. This study aimed to evaluate chromogranin A (CgA), a known SAM activation marker, in saliva samples from laboratory dogs when the SAM response was pharmacologically induced. A selective noradrenaline transporter blocker, atomoxetine, was orally administered without causing any adverse responses in dogs to see if it increases salivary CgA. Three treatment groups were designed to determine whether CgA was increased only in the treatment with atomoxetine compared to a placebo or with pre-administration of dexmedetomidine followed by atomoxetine. Dexmedetomidine was included in the study because it is a selective alpha-2 adrenoreceptor agonist that inhibits central noradrenaline activity. The results were found to be consistent with our hypothesis and suggest that salivary CgA correlates with central noradrenaline activity, indicating that it can be a useful marker to assess SAM activity in dogs. Abstract Since salivary chromogranin A (CgA) is one of the known sympathetic adrenomedullar system (SAM) stress markers in humans and pigs, this study aimed to investigate whether salivary CgA in dogs reflects SAM activation. Our hypothesis was that salivary CgA would increase when central noradrenaline was pharmacologically induced. A selective noradrenaline transporter blocker, atomoxetine, was orally administered without causing any aversive responses in nine laboratory dogs to see if it would increase salivary CgA. Three treatment groups (i.e., atomoxetine, placebo, and pre-administration of a selective alpha-2 adrenoreceptor agonist (dexmedetomidine) followed by atomoxetine) were prepared with a randomized crossover design. Saliva sample collection, heart rate measurement and behavior observation were performed at Time 0 (baseline) and at 30, 60, 90 and 150 min after each treatment administration. The results demonstrated that salivary CgA significantly increased at 90 min in the atomoxetine treatment (p < 0.05), whereas it was not observed in the other two treatments. The present study showed that salivary CgA was increased by atomoxetine-induced SAM activation. However, this increase was blocked if dexmedetomidine was pre-administered. Overall, the results indicate that salivary CgA is a potential candidate for SAM-mediated stress markers in dogs. Further study to determine the dynamics of salivary CgA will be helpful in its practical use.