Physiological Responses to Olfactory Trace Amine Receptor Activation

Abstract: Trace amines are endogenous compounds detected by G protein-coupled receptors called trace amine-associated receptors (TAARs) that are present in the brain, peripheral organs, and the olfactory system. Olfactory TAARs are selectively activated by ligands from diverse ecological sources, including 2-phenylethylamine (PE; carnivore urine, activates TAAR4), isoamylamine (IA; spoilt food, also present in urine, activates TAAR3) and trimethylamine (TMA; a putative murine pheromone, activates TAAR5). All compounds induce innate behaviours but the brain areas activated are largely unknown. Further, we have shown that these compounds readily cross cell membranes, allowing entry into the systemic circulation following inhalation, suggesting peripheral TAARs might also be involved in physiological responses following inhalation, but this has not previously been investigated. This study seeks to address these two knowledge gaps. For this, male mice were exposed to odours for 30 minutes and their behaviour was digitally recorded. Animals were euthanized 30 minutes after exposure and blood and organs were collected. All three compounds induced innate avoidance behaviours (PE P=0.03, IA P=0.0012, TMA P<0.0001) with only TMA significantly decreasing total locomotor activity (P=0.0029). PE significantly increased plasma corticosterone (P=0.0362), blood glucose (P=0.0473) and defecation (P=0.01). In contrast, TMA had no effect on these measures while IA increased blood glucose (P=0.021) and defecation (P=0.001). The PE responses are consistent with a fight-or-flight response as expected of a predator-associated odour, while the TAAR ligands associated with other ecological contexts induced different physiological responses, despite an apparently similar avoidance response. Together the results indicate that the TAAR system is useful for probing physiological responses to different ecological contexts. Current studies are examining the brain areas activated in response to each odour and whether the systemic responses are downstream of activation of olfactory TAARs, or secondary to the compound(s) entering the bloodstream and activating non-olfactory TAARs.

This seminar is presented in partial fulfillment of the requirements for the degree of Master of Science