Stress resilience-associated behaviors following predator scent stress are accompanied by upregulated nucleus accumbens mGlu5 transcription in female Sprague Dawley rats

Blount, Harrison; Dee, J.; Wu, Lizhen; Schwendt, Marek; Knackstedt, Lori A.

doi:10.1016/j.bbr.2022.114090

Cited by 8 publications

(9 citation statements)

References 82 publications

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“…Acute oxycodone is anxiolytic 22 and here we observe the same during short withdrawal from oxycodone (less than 24 h), potentially identifying anxiolysis as a factor underlying the motivation to consume both drugs. Sucrose is not anxiogenic in the present work, as this group’s EPM behavior is comparable to control (unstressed) rat behavior in other publications using the same procedures 51 , 52 . Thus, despite being assessed at the same time point following the last self-administration session, oxycodone and oxycodone + alcohol have different effects on SSW and anxiety-like behavior, likely due to distinct neurochemical and neuroanatomical regulating these behaviors during withdrawal 53 .…”

Section: Discussionsupporting

confidence: 78%

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking

Wilkinson,

Blount,

Davis

et al. 2023

Sci Rep

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Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with homecage access to alcohol (20% v/v) and/or water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent a cue-primed reinstatement test and brains were processed for c-fos mRNA expression. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, only female oxycodone + alcohol rats exhibited decreased demand elasticity and increased cue-primed reinstatement. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor expressing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.

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Section: Discussionsupporting

confidence: 78%

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking

Wilkinson,

Blount,

Davis

et al. 2023

Sci Rep

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“…Various levels of these dimensions were observed in all rats: some rats exhibited both, only one, or none. This variability is unsurprising and has been widely reported (Ritov et al, 2016;Blount et al, 2023), although the distribution of the different behaviors varies according to the type of stressor, the variables used, the experimental design, the strain of animals, etc. These results are in line with human observations showing a wide range of pathologies corresponding to our different groups, from resilient to partial or complete PTSD (Mota et al, 2016).…”

Section: Behavior During Mss Exposurementioning

confidence: 94%

Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes

Desnouveaux¹,

Poly²,

Edmond³

et al. 2023

Front. Neurosci.

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IntroductionDepending on the individual, exposure to an intense stressor may, or may not, lead to a stress-induced pathology. Predicting the physiopathological evolution in an individual is therefore an important challenge, at least for prevention. In this context, we developed an ethological model of simulated predator exposure in rats: we call this the multisensorial stress model (MSS). We hypothesized that: (i) MSS exposure can induce stress-induced phenotypes, and (ii) an electrocorticogram (ECoG) recorded before stress exposure can predict phenotypes observed after stress.MethodsForty-five Sprague Dawley rats were equipped with ECoG telemetry and divided into two groups. The Stress group (n = 23) was exposed to an MSS that combined synthetic fox feces odor deposited on filter paper, synthetic blood odor, and 22 kHz rodent distress calls; the Sham group (n = 22) was not exposed to any sensorial stimulus. Fifteen days after initial exposure, the two groups were re-exposed to a context that included a filter paper soaked with water as a traumatic object (TO) reminder. During this re-exposure, freezing behavior and avoidance of the filter paper were measured.ResultsThree behaviors were observed in the Stress group: 39% developed a fear memory phenotype (freezing, avoidance, and hyperreactivity); 26% developed avoidance and anhedonia; and 35% made a full recovery. We also identified pre-stress ECoG biomarkers that accurately predicted cluster membership. Decreased chronic 24 h frontal Low θ relative power was associated with resilience; increased frontal Low θ relative power was associated with fear memory; and decreased parietal β2 frequency was associated with the avoidant-anhedonic phenotype.DiscussionThese predictive biomarkers open the way to preventive medicine for stress-induced diseases.

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“…Exposure sessions were recorded to measure time spent freezing. Immediately after TMT/control exposure, vaginal lavage was used to collect samples to determine the estrous cycle phase (estrus, pro-estrus, or met/diestrus), as described in Blount et al [32].…”

Section: Stress Exposurementioning

confidence: 99%

“…Quantification of brain monoamines via ex vivo tissue punch analysis following footshock, forced swim, social defeat/isolation, predator/predator scent, and chronic/repeated stress find disrupted monoamine system function in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and hippocampus (HIPP) associated with stress exposure [24][25][26][27][28] and stress-susceptibility [25,[29][30][31]. Since PTSD is more prevalent in women and preclinical research indicates sex-specific alterations in stress susceptibility in rodents [32], examining the long-term effect of stress on brain monoamines in stress-Susceptible female rats is imperative.…”

Section: Introductionmentioning

confidence: 99%

Brain Monoamine Dysfunction in Response to Predator Scent Stress Accompanies Stress-Susceptibility in Female Rats

et al. 2023

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Post-traumatic stress disorder (PTSD) is prevalent in women; however, preclinical research on PTSD has predominantly been conducted in male animals. Using a predator scent stress (PSS) rodent model of PTSD, we sought to determine if stress-susceptible female rats show altered monoamine concentrations in brain regions associated with PTSD: the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and dorsal (dHIPP) and ventral (vHIPP) hippocampus. Female Sprague–Dawley rats were exposed to a single, 10-min PSS exposure and tested for persistent anhedonia, fear, and anxiety-like behavior over four weeks. Rats were phenotyped as stress-susceptible based on sucrose consumption in the sucrose preference task and time spent in the open arms of the elevated plus maze. Brain tissue was collected, and norepinephrine, dopamine, serotonin, and their metabolites were quantified using high-performance liquid chromatography. Stress-susceptibility in female rats was associated with increased dopamine and serotonin turnover in the mPFC. Susceptibility was also associated with elevated dopamine turnover in the NAc and increased norepinephrine in the vHIPP. Our findings suggest that stress-susceptibility after a single stress exposure is associated with long-term effects on monoamine function in female rats. These data suggest interventions that decrease monoamine turnover, such as MAOIs, may be effective in the treatment of PTSD in women.

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Stress resilience-associated behaviors following predator scent stress are accompanied by upregulated nucleus accumbens mGlu5 transcription in female Sprague Dawley rats

Cited by 8 publications

References 82 publications

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking

Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes

Brain Monoamine Dysfunction in Response to Predator Scent Stress Accompanies Stress-Susceptibility in Female Rats

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