Freezing to the predator odor 2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is disrupted by olfactory bulb removal but not trigeminal deafferentation

Behav Brain Res. 2013 Sep 15;253:54-9. doi: 10.1016/j.bbr.2013.06.034. Epub 2013 Jul 4.


2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is a synthesized component of red fox anal secretions that reliably elicits defensive behaviors in rats and mice. TMT differs from other predator odors because it is a single molecule, it can be synthesized in large quantities, and the dose for exposure is highly controllable in an experimental setting. TMT has become a popular tool for studying the brain mechanisms that mediate innate fear behavior to olfactory stimuli. However, this view of TMT as a biologically relevant olfactory stimulus has been challenged by suggestions that the odor elicits fear behavior due to its irritating properties, presumably working through a nociceptive mechanism. To address this criticism our lab measured freezing behavior in rats during exposures to 2 odors (TMT and butyric acid) and H2O (no odor control) following either surgical transection of the trigeminal nerves or ablation of the olfactory bulbs. Our findings (Experiment 1) indicate that freezing behavior to TMT requires an intact olfactory system, as indicated by the loss of freezing following olfactory bulb removal. Experiment 2 revealed that rats with trigeminal nerve transection freeze normally to TMT, suggesting the olfactory system mediates this behavior to TMT. A replication of Experiment 1 that included contextual fear conditioning revealed that the decreased freezing behavior was not due to an inability of olfactory bulb ablated rats to freeze (Experiment 3). Taken together, these findings support TMT's role as an ecologically relevant predator odor useful in experiments of unconditioned fear that is mediated via olfaction and not nociception.

Keywords: Butyric acid; Olfactory bulb; Predator odor; TMT; Trigeminal nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Butyric Acid / pharmacology
  • Denervation
  • Fear / physiology
  • Freezing Reaction, Cataleptic / drug effects*
  • Male
  • Motor Activity / drug effects
  • Neurons, Afferent / physiology*
  • Odorants*
  • Olfactory Bulb / physiology*
  • Predatory Behavior
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Thiazoles / pharmacology*
  • Trigeminal Nerve / physiology*


  • 2,5-dihydro-2,4,5-trimethylthiazoline
  • Thiazoles
  • Butyric Acid