The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric illness that can increase the risk for developing an alcohol use disorder (AUD). While clinical data has been useful in identifying similarities in the neurobiological bases of these disorders, preclinical models are essential for understanding the mechanism(s) by which PTSD increases the risk of developing AUD. The purpose of these studies was to examine if exposure of male Long-Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5trimethylthiazoline (TMT) would increase alcohol self-administration, potentially by facilitating transfer of salience towards cues, and alter neuronal response to alcohol as measured by the immediate early gene c-Fos. In Experiment 1 rats exposed to repeated (4x) TMT showed reductions in goal-tracking behavior in Pavlovian conditioned approach, and increases in alcohol self-administration. In Experiment 2 rats exposed to repeated TMT showed blunted basolateral amygdala c-Fos response to alcohol, and increased correlation between medial prefrontal cortex and amygdala subregions. In Experiment 3 rats exposed to single, but not repeated TMT showed increases in alcohol self-administration, and no change in anxiety-like behavior or hyperarousal. In Experiment 4, rats showed no habituation of corticosterone response after 4 TMT exposures. In summary, exposure of male rats to TMT can cause escalations in alcohol self-administration, reductions in goal-tracking behavior, and reduction in BLA response to alcohol. These studies outline and utilize a novel preclinical model that can be used to further neurobiological understanding of the relationship between PTSD and AUD.

RETRACTED: Alcohol drinking alters stress response to predator odor via BNST kappa opioid receptor signaling in male mice

“…Since we chose to not use another cohort of surgerized/transgenic mice for testing in the EPM, it is important to note that testing without prior TMT exposure was a limitation. TMT can have mixed effects on time spent in the open arms of the EPM, which can be dependent on the TMT concentration ( Hacquemand et al, 2013 ; McGregor et al, 2002 ; Makhijani et al, 2020 ). This points to the EPM as a distinct, novelty-related probe, which may not be robust to differentiate EtOH-related phenotypes after a confounding TMT exposure.…”

The effects of predator odor (TMT) exposure and mGlu3NAM pretreatment on lasting behavioral and molecular adaptations in the insular cortex and BNST

“…Animal models have used exposure to the scent of a predator as a stressor that produces lasting behavioral consequences with relevance to stress-related neuropsychiatric disorders [42][43][44][45][46][47][48][49][50][51][52][53][54][55]. For example, exposure to the synthetically derived fox odor 2,5 dihydro 2,4,5 trimethylthiazoline (TMT) produces avoidance and freezing behaviors, indicative of a fear like response and increased serum corticosterone, reflecting a stress response [47,50,56,57]. Other studies have showed lasting anxiety like and hyperarousal behavior, as well as avoidance of a TMT paired context or cue [43,51].…”