Trimethylthiazoline (TMT) supports conditioned flavor avoidance and activates viscerosensory, hypothalamic, and limbic circuits in rats

Abstract

Interoceptive stimuli modulate stress responses and emotional state, in part, via ascending viscerosensory inputs to the hypothalamus and limbic forebrain. It is unclear whether similar viscerosensory pathways are recruited by emotionally salient exteroceptive stimuli, such as odors. To address this question, we investigated conditioned avoidance and central cFos activation patterns in rats exposed to synthetic trimethylthiazoline (TMT), an odiferous natural component of fox feces. Experiment 1 demonstrated that rats avoid consuming novel flavors that previously were paired with TMT exposure, evidence that TMT supports conditioned flavor avoidance. Experiment 2 examined central neural systems activated by TMT. Odor-naïve rats were acutely exposed to low or high levels of TMT or a novel non-aversive control odor and were perfused with fixative 60-90 minutes later. A subset of rats received retrograde neural tracer injections into the central nucleus of the amygdala (CeA) 7-10 days before odor exposure and perfusion. Brain sections were processed for dual immunocytochemical detection of cFos and other markers to identify noradrenergic (NA) neurons, CRH neurons, and retrogradely labeled neurons projecting to the CeA. Significantly greater proportions of medullary and pontine NA neurons, hypothalamic CRH neurons, and CeA-projecting neurons were activated in rats exposed to TMT compared to activation in rats exposed to the non-aversive control odor. Thus, the ability of TMT to support conditioned avoidance behavior is correlated with significant odor-induced recruitment of hypothalamic CRH neurons and brainstem viscerosensory inputs to the CeA. Supported by National Institutes of Health grant #MH01208

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