The effects of predator odor (TMT) exposure and mGlu3 NAM pretreatment on behavioral and NMDA receptor adaptations in the brain

Tyler, Ryan E.; Bluitt, Maya N.; Engers, Julie L.; Lindsley, Craig W.; Besheer, Joyce

doi:10.1016/j.neuropharm.2022.108943

Cited by 13 publications

(18 citation statements)

References 89 publications

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“…Nevertheless, visual comparison of groups shows some striking differences that may suggest that alcohol experience affects behavioral responses to a predator odor stressor. Both cohorts showed increased digging behavior in the TMT group, consistent with previous work [39, 60]. However, the alcohol-experienced cohort engaged in digging behavior to a greater extent than the alcohol-naïve cohort.…”

Section: Discussionsupporting

confidence: 90%

“…Gat-1 is the gene that encodes the GABA neurotransmitter transporter protein (GAD-1), which suggests altered GABA neurotransmitter levels in the synapse in the Acb. Prior data have shown increased NMDA receptor gene expression in the aIC 2 weeks after TMT [60], suggesting increased excitatory signaling in the aIC. As such, increased Gad-1 expression in the aIC observed here may be the result of compensatory increase of local, GABAergic inhibition onto excitatory cells to restore changes in excitatory/inhibitory ratio [65].…”

Section: Discussionmentioning

confidence: 99%

“…TMT Exposure Behavior -Analysis of TMT exposure behaviors are identical to [39,40,60]. The length of the TMT exposure chamber (rectangular) was divided in the middle into two compartments for analysis (TMT side and non-TMT side) using ANY-maze software.…”

Section: Discussionmentioning

confidence: 99%

“…Predator Odor Exposure TMT Exposure -2,5-dihydro-2,4,5-trimethylthiazoline (TMT) exposure test chambers and experimental set-up were identical to those used in [39,40,60]. Briefly, rats were transported from the vivarium in the home cage to a separate, well-ventilated room that contained the test chambers in which rats were exposed to TMT (45.72 × 17.78 × 21.59 cm; UNC Instrument Shop, Chapel Hill, NC).…”

Section: Methodological Details Operant Drug Discriminationmentioning

confidence: 99%

“…The length of the back wall of the test chambers was opaque white with two opaque black side walls and a clear, plexiglass front wall to enable video recordings and a clear sliding lid. The bottom of the chamber was covered with a layer of white bedding (approximately 1200 ml) [39, 40, 60] except for the c-Fos experiment (Experiment 2) in which no bedding was present. A small, metal basket was hung on the right-side wall (17.8 cm above the floor) to hold a piece of filter paper.…”

Section: Methodsmentioning

confidence: 99%

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Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Tyler

Bluitt

Voorhies

et al. 2022

Preprint

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Post-traumatic stress disorder (PTSD) confers enhanced vulnerability to develop comorbid alcohol use disorder (AUD). Exposure to the scent of a predator, such as the fox odor TMT, has been used to model a traumatic stressor with relevance to PTSD symptomatology. Alcohol produces distinct interoceptive (subjective) effects that may influence vulnerability to problem drinking and AUD. As such, understanding the lasting impact of stressor on sensitivity to the interoceptive effects of alcohol is clinically relevant. The present study used a 2-lever, operant drug discrimination procedure to train male, Long-Evans rats to discriminate the interoceptive effects of alcohol (2 g/kg, IG) from water. Upon stable performance, rats underwent a 15-min exposure to TMT. Two weeks later, an alcohol dose-response curve was conducted to evaluate the lasting effects of the TMT stressor on the interoceptive effects of alcohol. The TMT group showed a leftward shift in ED50 of the dose response curve compared to controls, reflecting potentiated interoceptive sensitivity to alcohol. TMT exposure did not affect response rate. GABAergic signaling in both the anterior insular cortex (aIC) and the nucleus accumbens (Acb) is involved in the interoceptive effects of alcohol and stressor-induced adaptations. As such, follow-up experiments in alcohol-naive rats examined neuronal activation (as measured by c-Fos immunoreactivity) following TMT and showed that TMT exposure increased c-Fos expression in the aIC and the nucleus accumbens core (AcbC). 2 weeks after TMT exposure, Gad-1 gene expression was elevated in the aIC and Gat-1 was increased in the Acb compared to controls. Lastly, the alcohol discrimination and alcohol-naive groups displayed dramatic differences in stress reactive behaviors during the TMT exposure, suggesting that alcohol exposure may alter the behavioral response to predator odor. Together, these data suggest that predator odor stressor results in potentiated sensitivity to alcohol possibly through GABAergic adaptations in the aIC and Acb, which may be relevant to understanding PTSD-AUD comorbidity.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodological Details Operant Drug Discriminationmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Tyler

Bluitt

Voorhies

et al. 2022

Preprint

Self Cite

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Predator Odor Stressor, 2,3,5‐Trimethyl‐3‐Thiazoline (TMT): Assessment of Stress Reactive Behaviors During an Animal Model of Traumatic Stress in Rats

Ornelas,

Besheer

2024

Current Protocols

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Animal models utilizing predator odor stress are important in understanding implications for post‐traumatic stress disorder. 2,5‐dihydro‐2,4,5‐trimethylthiazoline (TMT) has been used to measure stress reactive behaviors during TMT exposure, indicative of stress coping behaviors. In addition, long‐term consequences of stress including contextual‐induced stress memory, anxiety‐like and hyperarousal behaviors, and subsequent increases in alcohol self‐administration can also be examined after TMT exposure. In this article, we describe the TMT exposure protocol used in our lab and how we measure different stress‐reactive behaviors that rats engage in during the TMT exposure. Rats are placed in Plexiglass chambers that contain white bedding on the bottom of the chamber and a metal basket in the top right corner containing a filter paper that 10 µl of TMT is pipetted onto. During the 10 min exposure, rats can move around the chamber freely. Exposures are recorded by a video camera for later analysis. During TMT exposure, rats engage in a variety of stress‐reactive behaviors, including digging and immobility behavior. These are two distinctly different types of stress‐induced behavioral coping strategies to measure individual differences in stress responsivity. To examine individual differences, we group rats into TMT‐subgroups based on time spent engaging in digging or immobility behavior. We calculate a digging/immobility ratio score in which we divide the total time spent digging by the total time spent immobile. A cut‐off strategy is used such that rats with a criterion ratio score <1.0 are classified as TMT‐1 (i.e., low digging/high immobility; greater passive coping) and rats with a ratio score >1.0 are classified as TMT‐2 (i.e., high digging/low immobility; greater active coping). Here, we provide a detailed description of the TMT exposure protocol and step‐by‐step process in evaluation of stress‐reactive behaviors. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Predator odor stressor exposure using TMTBasic Protocol 2: Description of stress‐reactive behaviors during TMT exposure and formation of TMT‐subgroups

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The role of mGlu receptors in susceptibility to stress-induced anhedonia, fear, and anxiety-like behavior

Modrak¹,

Wilkinson²,

Blount³

et al. 2023

International Review of Neurobiology

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The effects of predator odor (TMT) exposure and mGlu3 NAM pretreatment on behavioral and NMDA receptor adaptations in the brain

Cited by 13 publications

References 89 publications

Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

Predator Odor Stressor, 2,3,5‐Trimethyl‐3‐Thiazoline (TMT): Assessment of Stress Reactive Behaviors During an Animal Model of Traumatic Stress in Rats

The role of mGlu receptors in susceptibility to stress-induced anhedonia, fear, and anxiety-like behavior

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