SB-258585 reduces food motivation while blocking 5-HT6 receptors in the non-human primate striatum.

The interest in new 5-HT6 agents stems from their ability to modulate cognition processing, food motivation and anxiety-like behaviors. While these findings come primarily from rodent studies, no studies on primates have been published. Furthermore, our understanding of where and how they act in the brain remains limited. Although the striatum is involved in all of these processes and expresses the highest levels of 5-HT6 receptors, few studies have focused on it. We thus hypothesized that 5-HT6 receptor blockade would influence food motivation and modulate behavioral expression in non-human primates through striatal 5-HT6 receptors. This study thus aimed to determine the effects of acute administration of the SB-258585 selective 5-HT6 receptor antagonist on the feeding motivation and behaviors of six male macaques. Additionally, we investigated potential 5-HT6 targets using PET imaging to measure 5-HT6 receptor occupancy throughout the brain and striatal subregions. We used a food-choice task paired with spontaneous behavioral observations, checking 5-HT6 receptor occupancy with the specific PET imaging [18F]2FNQ1P radioligand. We demonstrated, for the first time in non-human primates, that modulation of 5-HT6 transmission, most likely through the striatum (the putamen and caudate nucleus), significantly reduces food motivation while exhibiting variable, weaker effects on behavior. While these results are consistent with the literature showing a decrease in food intake in rodents and proposing that 5-HT6 receptor antagonists can be used in obesity treatment, they question the antagonists' anxiolytic potential.

Evaluation of the practical clinical use of the Horse Grimace Scale translated into French.

OBJECTIVE: To assess the reliability of a French version of the Horse Grimace Scale (HGSfv). STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: The operated (OP) group included 13 horses undergoing elective surgery. The positive (PC) and negative control (NC) groups included seven colicking horses and eight exercising sport horses, respectively. METHODS: Photographs were extracted from videos of the horses' heads. Videos were taken before and immediately after surgery in OP, on arrival of the horse in PC, and at rest in their stalls in NC. Pictures were evaluated by three anaesthetists [Diplomates (DIPs)] and four riders (RIDs) using Horse Grimace Scale translated into French (HGSfv) at two points, 2 weeks apart (E1 and E2). Each evaluator gave each image a score (1-3) for six identified facial action units. The scores given by DIPs and RIDs were compared using a Wilcoxon test. Intra- and inter-evaluator reliability were assessed using Spearman correlation tests (rs) and intra-class coefficients (ICCs), respectively. RESULTS: RIDs and DIPs gave significantly higher scores in the PC group than in the NC group [RIDsE1PC 5.0 (4.2-9.8) versus RIDsE1NC 2.2 (0.0-6.5), p = 0.02; RIDsE2PC 5.2 (3.2-9.5) versus RIDsE2NC 2.0 (0.2-5.8), p < 0.01; DIPsE1PC 4.0 (1.3-6.3) versus DIPsE1NC 2.2 (1.0-4.7), p = 0.04; DIPsE2PC 2.7 (1.0-6.0) versus DIPsE2NC 1.0 (0.0-2.3), p = 0.03]. Scores given by RID or DIPs 2 weeks apart were highly correlated [rs (RIDsE1, RIDsE2) r = 0.86, p < 0.0001] and [rs (DIPsE1, DIPsE2) r = 0.81 p < 0.0001]. The ICC between RIDs and DIPs in E1 and E2 was 0.94 (0.92-0.95) and 0.91 (0.89-0.93), respectively. The specificity and sensitivity of the HGSfv was 94% and 43%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Using the HGSfv, knowledge of horses rather than specialization in veterinary anaesthesia and analgesia appears to differentiate horses with visceral pain from those assumed to be pain free.