Abstract
Animal welfare assessment requires measures for positive affective state. Pharmacological agents that manipulate affective state can be used to evaluate novel biomarkers for affective state assessment. However, to validate that an agent has modified brain function, a reliable indicator is required. Circulating cortisol has been used as a reporter for effective delivery of the antidepressant selective serotonin reuptake inhibitor (SSRI) fluoxetine hydrochloride to the brain in humans and sheep. Here, we tested cortisol as a reporter for effective delivery of fluoxetine hydrochloride to the pig brain. We hypothesized that following administration of SSRI, innervation of the serotonergic reward pathway would result in activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased circulating cortisol levels. Large White-Landrace gilts received either a single intravenous dose of 100 mg fluoxetine hydrochloride suspended in 10 mL saline (n = 4), or 10 mL saline alone (n = 4). Blood samples were collected every 15 min for one hour prior to, and six hours post-treatment. The interaction of treatment x time on mean plasma cortisol levels between 15-165 min post-treatment was significant (p = 0.048) with highest cortisol concentrations of SSRI treated pigs versus controls (+ 98%) at 135 min post-treatment. However, individual cortisol profiles after SSRI treatment revealed high inter-individual variation in response. We conclude that, while combined data imply that plasma cortisol may be a readout for SSRI efficacy, inter-individual variation in SSRI response may preclude application of this approach in the pig. Given the current limited sample size, further research to confirm these findings is needed.
Highlights
The assessment of animal affective state can be challenging, in particular the evaluation of positive states
We tested whether measurement of circulating cortisol levels could be used as a reliable indicator of effective delivery of selective serotonin reuptake inhibitors (SSRI) to the pig brain
We observed a substantial increase in mean plasma cortisol levels after SSRI treatment 15–165 min post-treatment as compared with saline controls
Summary
The assessment of animal affective state can be challenging, in particular the evaluation of positive states. Behavioral measures and affective bias tests are the predominant assessment methods for positive states [1]. These methods are less suited to a production environment, because they are time-consuming and arguably subjective [2,3]. There is, an urgent need to identify and validate novel physiological and molecular markers of positive affect, such as miRNA [4,5], to complement or even replace behavioral [6] measures. Validation of novel biomarkers for affective state requires robust means to manipulate affective state in a consistent manner. In order to use SSRI in validation experiments of novel biomarkers, a measure that demonstrates the effective delivery of the SSRI to the brain is required. No such data are available for the pig
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