Biology subjects

Ornelas, L. C.

Publications and source records attributed to Ornelas, L. C..

6 recordsLinked to original sources

bioRxiv2024

The persistent effects of predator odor stressor enhance interoceptive sensitivity to alcohol through GABA-A receptor adaptations in the prelimbic cortex in male, but not female rats

BackgroundTraumatic stress is associated with high rates of problematic alcohol use, but how the persistent effects of trauma impact sensitivity to alcohol remain unknown. This study examined the persistent effects of traumatic stress exposure on sensitivity to alcohol and underlying neurobiological mechanisms in rats. MethodsMale (N=98) and female (N=98) Long-Evans rats were exposed to the predator odor TMT, and two weeks later, molecular, neuronal, and behavioral sensitivity to alcohol were assessed. Next, rats were trained to discriminate alcohol from water (male N=70; female N=56), and the impact of TMT on interoceptive sensitivity to alcohol and the alcohol-like effects of systemic GABAA receptor activation were evaluated. Lastly, functional involvement of GABAA and NMDA receptors in the prelimbic cortex (PrL) and the anterior insular cortex (aIC) was investigated. ResultsTMT exposure sex-dependently altered PrL Gabra1, and elevated aIC Grin2b and Grin2c in males. TMT increased PrL c-Fos in males, which was attenuated by alcohol administration. Alcohol-induced locomotor and startle response effects were attenuated in the TMT group in both sexes. TMT exposure potentiated interoceptive sensitivity to alcohol in males but not in females, and this effect was driven by GABAA receptors in the PrL. Greater stress reactivity during TMT exposure was associated with higher interoceptive sensitivity to alcohol, and alcohol exposure history was linked to a heightened stress response to TMT in males. ConclusionsTraumatic stress increased interoceptive sensitivity to alcohol in males, but not females, through PrL GABAA receptor adaptations, potentially enhancing the stimulatory, and by extension the rewarding, effects of alcohol.

neuroscience↗

bioRxiv2023

Predator Odor Stressor, 2,3,5-trimethyl-3-thiazoline (TMT): Assessment of stress reactive behaviors during an animal model of traumatic stress in rats

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 Plexiglas chambers that contains white bedding on the bottom of the chamber and a metal basket in the top right corner that contains a filter paper on which 10 {micro}L 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 below 1.0 are classified as TMT-1 (i.e., low digging/high immobility; greater passive coping) and rats with a ratio score above 1.0 are classified as TMT-2 (i.e., high digging/low immobility; greater active coping). In the present paper, we provide a detailed description of the TMT exposure protocol and step- by-step process in evaluation of stress-reactive behaviors. Basic Protocol 1: Predator Odor Stressor Exposure using TMT Basic Protocol 2: Description of Stress-Reactive Behaviors during TMT Exposure and Formation of TMT-subgroups

animal behavior and cognition↗

bioRxiv2023

The impact of prenatal alcohol and synthetic cannabinoid exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood. Importantly, we find that prenatal alcohol exposure (PAE) caused lower baseline corticosterone levels in adolescent males and females. Co-exposure to alcohol + CP produced hyperactivity during open field test in males, but not females. During the two-bottle choice alcohol-drinking procedure, prenatal cannabinoid exposed male and female adolescent rats drank more alcohol than their vehicle-exposed controls. In adulthood, female rats treated with prenatal cannabinoid exposure (PCE), showed an overall total increase in alcohol intake during alcohol self-administration; but this was not found in males. When the reinforcer was changed to a 1% sucrose solution, male rats exposed to PCE, showed a reduced self-administration compared to vehicle-exposed males, potentially indicative of an anhedonic response. This lower self-administration persisted when 20% alcohol was reintroduced to the sucrose solution. Lastly, following an abstinence period, there were no changes due to prenatal drug exposure in either males or females. Overall, these data suggest lasting consequences of prenatal alcohol and cannabinoid exposure during adolescence and adulthood in male and female rats.

animal behavior and cognition↗

bioRxiv2022

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

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, i.g.) 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.

neuroscience↗

bioRxiv2021

The Role of the Nucleus Reuniens in Regulating Contextual Conditioning with the Predator Odor TMT

RationaleExperiencing intrusive distressing memories of a traumatic event(s) is a prominent symptom profile for post-traumatic stress disorder (PTSD). Understanding the neurobiological mechanisms associated with this symptom profile can be invaluable for effective treatment for PTSD. ObjectivesHere, we investigated the functional role of the nucleus reuniens (RE), a midline thalamic in modulating stressor-related memory. MethodsFemale Long Evans rats were implanted with a cannula aimed at the RE. The RE was pharmacologically inactivated via muscimol (0.5 mM) prior to exposure to the predator odor stressor trimethylthiazoline (TMT; synthetically derived fox feces component) or water (controls) in a distinct context with bedding material (Experiment 1) or no bedding (Experiment 2). To measure context reactivity, the index of the contextual memory, 2 weeks following exposure to TMT, rats were re-exposed to the TMT-paired context (in the absence of TMT). ResultsIn Experiment 1, during context re-exposure (with bedding), inactivation of the RE had no effect on context reactivity. In Experiment 2, during context re-exposure (no bedding), rats previous exposed to TMT showed decreased immobility compared to controls, indicating reactivity to the context and likely related to increased exploration of the environment. Rats in the TMT group that received RE inactivation showed increased immobility relative to rats that received aCSF, suggesting that muscimol pre-treatment blunted context reactivity. ConclusionIn conclusion, recruitment of the RE in stressor-related contextual memory appears to be dependent on the contextual environment and whether the animal is able to engage in different stress coping strategies.

neuroscience↗

bioRxiv2020

Increased alcohol self-administration following exposure to the predator odor TMT in high stress-reactive female rats

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid. Additionally, individual differences in response to stress suggest resilient and susceptible populations. The current study exposed male and female Long Evans rats to the synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to examine individual differences in stress-reactive behaviors (digging and immobility) and whether these differences could predict lasting consequences of TMT and increases in alcohol drinking. Male and female Long Evans rats were trained on operant alcohol self-administration. After 9 sessions, rats underwent exposure to TMT or water (Control) in a distinct context. 6 days after TMT exposure, rats underwent re-exposure to the TMT-paired context (without TMT), and a series of behavioral assessments (acoustic startle, zero maze, light/dark box), after which rats resumed alcohol self-administration. Rats were divided into two TMT-subgroups using a ratio of digging and immobility behavior during TMT exposure: TMT-subgroup 1 (low digging/immobility ratio) and TMT-subgroup 2 (high digging/immobility ratio). Digging/immobility ratio scores predicted elevated corticosterone levels during TMT exposure and reactivity during context re-exposure in males and females (TMT-subgroup 2), as well as elevated corticosterone levels after context re-exposure and hyperarousal behavior in females (TMT-subgroup 1). Furthermore, TMT stress reactivity predicted increases in alcohol self-administration, specifically in females. These data show that stress-reactivity can predict lasting behavioral changes which may lead to a better understanding of increases in alcohol drinking following stress in females and that individual differences in stress-reactive behaviors using TMT may be helpful to understand resilience/susceptibility to the lasting consequences of stress. HighlightsO_LIExposure to the predator odor TMT produces distinct behavioral phenotypes in male and female rats C_LIO_LIMale and female high stress reactive rats show enhanced reactivity to the TMT-paired context C_LIO_LIStress-reactivity during TMT predicts increases in alcohol self-administration, in females C_LIO_LIStress-reactivity may help to understand resilience/susceptibility and impact on alcohol drinking C_LI

animal behavior and cognition↗