Oxytocin Reduces Sensitized Stress–Induced Alcohol Relapse in a Model of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity

Becker, Howard C.; López, Marcelo F.; King, Courtney; Griffin, William C.

doi:10.1016/j.biopsych.2022.12.003

Cited by 10 publications

(4 citation statements)

References 84 publications

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“…These data suggest sex differences in expression of proteins that regulate stress responses, in a key region implicated in PTSD ( Alavi et al, 2022 ). Predator odor exposure using TMT has also been used to examine individual differences in response to stress, as well as a rat model of comorbid PTSD and substance use disorders including cocaine use disorder ( Schwendt et al, 2018 ; Brodnik et al, 2017 , 2020 ) and AUD ( Ornelas et al, 2021a ; King and Becker, 2019 ; Becker et al, 2023 ). For example, Brodnik et al (2017) exposed male Sprague-Dawley rats to TMT then sub-grouped rats into a “susceptible” group based on time spent in open arms during elevated plus maze and avoidance behavior when re-exposed to the odor-paired context ( Brodnik et al, 2017 ).…”

Section: Stress Reactivity: Individual Differences and Implications F...mentioning

confidence: 99%

Predator odor stress reactivity, alcohol drinking and the endocannabinoid system

Ornelas,

Besheer

2024

Neurobiology of Stress

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Section: Stress Reactivity: Individual Differences and Implications F...mentioning

confidence: 99%

Predator odor stress reactivity, alcohol drinking and the endocannabinoid system

Ornelas,

Besheer

2024

Neurobiology of Stress

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“…Predator odor stressor exposure can also be used to investigate the complex interaction between increased alcohol consumption and stress, which may help in understanding the neurobiology associated with comorbid PTSD and alcohol use disorder (Ornelas, Tyler et al., 2021; Weera et al., 2020). For example, several studies have shown increased alcohol drinking (Alavi et al., 2022; Albrechet‐Souza et al., 2020; Makhijani et al., 2021) or alcohol relapse‐like behavior (Becker et al., 2023; King & Becker, 2019) following exposure to varying predator odor stressors, including TMT. Importantly, not all individuals who experience a traumatic event develop PTSD.…”

Section: Introductionmentioning

confidence: 99%

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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“…Oxytocin release in the central nucleus of the amygdala has also been shown to gate fear responses in rodents [ 17 – 19 ], and systemic oxytocin administration has been shown to reduce alcohol drinking in a novel rodent model of comorbid post-traumatic stress disorder and alcohol use disorder [ 20 ]. In humans, studies have shown that intranasal oxytocin is effective at reducing subjective ratings related to social anxiety [ 21 ] and depression [ 22 ] when used as an adjunct to exposure therapy and escitalopram treatment, respectively.…”

Section: Introductionmentioning

confidence: 99%

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

Nisbett,

Vendruscolo,

Koob

2024

Transl Psychiatry

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Mood and anxiety disorders are leading causes of disability worldwide and are major contributors to the global burden of diseases. Neuropeptides, such as oxytocin and opioid peptides, are important for emotion regulation. Previous studies have demonstrated that oxytocin reduced depression- and anxiety-like behavior in male and female mice, and opioid receptor activation reduced depression-like behavior. However, it remains unclear whether the endogenous opioid system interacts with the oxytocin system to facilitate emotion regulation in male and female mice. We hypothesized that opioid receptor blockade would inhibit the anxiolytic- and antidepressant-like effects of oxytocin. In this study, we systemically administered naloxone, a preferential μ−opioid receptor antagonist, and then intracerebroventricularly administered oxytocin. We then tested mice on the elevated zero maze and the tail suspension tests, respective tests of anxiety- and depression-like behavior. Contrary to our initial hypothesis, naloxone potentiated the anxiolytic-like, but not the antidepressant-like, effect of oxytocin. Using a selective μ−opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, and a selective κ−opioid receptor antagonist, norbinaltorphimine, we demonstrate that μ−opioid receptor blockade potentiated the anxiolytic-like effect of oxytocin, whereas κ−opioid receptor blockade inhibited the oxytocin-induced anxiolytic-like effects. The present results suggest that endogenous opioids can regulate the oxytocin system to modulate anxiety-like behavior. Potential clinical implications of these findings are discussed.

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Oxytocin Reduces Sensitized Stress–Induced Alcohol Relapse in a Model of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity

Cited by 10 publications

References 84 publications

Predator odor stress reactivity, alcohol drinking and the endocannabinoid system

Predator odor stress reactivity, alcohol drinking and the endocannabinoid system

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

µ-Opioid receptor antagonism facilitates the anxiolytic-like effect of oxytocin in mice

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