Biology subjects

Weera, M. M.

Publications and source records attributed to Weera, M. M..

4 recordsLinked to original sources

bioRxiv2025

Repeated Binge-Like Alcohol Drinking Heightens Aggression in Mice

RationaleIn humans, alcohol drinking is a significant driver of violent behaviors such as assaults and homicides. While acute intoxication is known to produce heightened aggression, little is known about alcohols long-term effects. Emerging evidence, however, suggests that chronic alcohol intake can promote heightened aggression, including during abstinence and may also sensitize individuals to alcohols acute aggression-heightening effects. ObjectivesThe goal of this study was to test the effects of chronic binge-like ethanol drinking on both alcohol-involved and alcohol-uninvolved aggression in male CFW mice. We aimed to model individual differences in binge drinking and assess changes in aggression during both acute and protracted abstinence. ResultsAfter 5 weeks of Drinking in the Dark (DID), CFW mice that showed higher levels of EtOH drinking ( high drinkers, 1.33 g/kg/h) became more aggressive than low drinkers (0.45 g/kg/h) and H2O controls, as measured via frequency of attack bites during resident-intruder fighting. In the first aggressive encounter following 1 week of abstinence, animals with an alcohol drinking history initiate a fight more rapidly and with greater consistency than H2O controls. We also found that a single session of binge-like alcohol drinking acutely heightened aggression regardless of drinking history. ConclusionsThese results suggest that repeated binge-like alcohol drinking causes escalations in alcohol-uninvolved aggression during acute (in high drinkers) and protracted abstinence (in all alcohol drinkers). However, chronic alcohol intake does not appear to sensitize animals to alcohol-involved aggression. These findings support the utility of genetically heterogeneous CFW mice for modeling individual variability in alcohol-related aggression.

neuroscience↗

bioRxiv2025

Predator odor stress produces sex- and subpopulation-specific increases in alcohol drinking, anxiety-like behavior, and lateral hypothalamic crh expression

Traumatic stress leads to maladaptive avoidance behaviors and alcohol misuse in some people. In rats, predator odor ("traumatic") stress produces persistent avoidance of stress-paired contexts and escalated alcohol self-administration in some animals (Avoiders), but not others (Non-Avoiders). This mirrors the individual differences in stress responsivity and alcohol misuse seen in humans. Here, we used a quinine-adulterated alcohol drinking procedure to model compulsive-like alcohol drinking in humans. Male and female Wistar rats were given 12 weeks of intermittent access to 20% (v/v) alcohol, followed by three weeks of limited access. Rats were then indexed for avoidance using predator odor stress exposure, and limited access drinking resumed for three additional weeks after stress. During this period, the alcohol solution was adulterated twice weekly with increasing concentrations of quinine. More Avoidant males were more resistant to quinine adulteration and Avoider males increased in non-quinine alcohol drinking. Using ultrasonic vocalizations (USVs) as a measure of affective state, we found that Non-Avoider males emitted more lower frequency USVs (<32 kHz) preceding, during, and following predator odor stress. Finally, quantification of crh, crhr1, crhr2, crhbp gene expression in the lateral hypothalamus revealed a strong positive correlation between greater crh transcripts and avoidance in males and a positive correlation between crh transcripts and less anxiety-like behaviors in females. Together, these results suggest that the intersection of stress and compulsive-like alcohol drinking is sex-specific and dependent on individual differences in stress outcomes. This work reinforces the importance of considering sex differences in stress and alcohol use disorder research. HighlightsO_LIMale Avoider rats show elevated two-bottle choice alcohol drinking after predator odor stress C_LIO_LIMore avoidant males show more aversion-resistant alcohol drinking C_LIO_LIFemale Avoider rats show heightened anxiety-like behavior 4 weeks after stress C_LIO_LILow frequency USVs predict Non-Avoider behavior in male rats C_LIO_LICrh expression in the LH is correlated with avoidance and alcohol drinking in male rats C_LI

neuroscience↗

bioRxiv2021

Cellular, physiological, and behavioral validation of a CRFR1:Cre-tdTomato transgenic rat for use in basic neuroscience research

Corticotropin-releasing factor type-1 (CRF1) receptors are critical to stress responses because they allow neurons to respond to CRF released in response to stress. Our understanding of the precise role of CRF1-expressing neuronal populations in CRF-mediated behaviors has been largely limited to mouse experiments due to the lack of genetic tools available to selectively visualize and manipulate CRF1+ cells in rats. Here, we describe the generation and validation of a transgenic CRF1:Cre-tdTomato rat, which expresses a bicistronic iCre-2A-tdTomato transgene directed by 200kb of promoter and enhacer sequence surrounding the Crhr1 cDNA present within a BAC clone, that has been transgenically inserted into the rat genome. We report that Crhr1 and Cre mRNA expression are highly colocalized in CRF1:Cre-tdTomato rats within both the central amygdala (CeA), composed of mostly GABAergic neurons, and in the basolateral amygdala (BLA), composed of mostly glutamatergic neurons. In the CeA, membrane properties, inhibitory synaptic transmission, and responses to CRF bath application in tdTomato+ neurons are similar to those previously reported in GFP+ cells in CRFR1-GFP mice. We show that stimulatory DREADD receptors can be selectively targeted to CeA CRF1+ cells via virally delivered Cre-dependent transgenes, that transfected Cre/tdTomato+ cells are activated by clozapine-n-oxide in vitro and in vivo, and that activation of these cells in vivo increases anxiety-like behavior and nocifensive responses. Given the accuracy of expression in the CRF1:Cre rat, modern genetic techniques used to investigate the anatomy, physiology, and behavioral function of CRF1+ neurons and circuits can now be performed in assays that require the use of rats as the model organism. Impact StatementA novel transgenic rat for studying the role of specific corticotropin-releasing factor type-1 receptor-expressing cell populations in physiology and behavior.

neuroscience↗

bioRxiv2019

THE ROLE OF CENTRAL AMYGDALA CORTICOTROPIN-RELEASING FACTOR IN PREDATOR ODOR STRESS-INDUCED AVOIDANCE BEHAVIOR AND ESCALATED ALCOHOL DRINKING IN RATS

Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity, and is highly co-morbid with alcohol use disorder (AUD). Our lab uses a predator odor (bobcat urine) stress model that produces conditioned avoidance of an odor-paired context in a subset of rats, mirroring avoidance symptoms that manifest in some but not all humans exposed to trauma. We previously showed that after predator odor stress, Avoiders exhibit escalated alcohol drinking, higher aversion-resistant operant alcohol responding, hyperalgesia, and greater anxiety-like behavior compared to unstressed Controls. We also showed that systemic antagonism of corticotropin-releasing factor-1 receptors (CRFR1) reduced escalation of alcohol drinking in rats not indexed for avoidance, that corticotropin-releasing factor (CRF) infusions into the central amygdala (CeA) produced conditioned place avoidance in stress-naive rats, and that intra-CeA infusion of a CRFR1 antagonist reduced hyperalgesia in Avoiders. Here, we show that avoidance behavior is persistent after repeated predator odor exposure and is resistant to extinction. In addition, Avoiders showed lower weight gain than Controls after predator odor re-exposure. In the brain, higher avoidance was correlated with higher number of c-Fos+ cells and CRF immunoreactivity in the CeA. Finally, we show that intra-CeA CRFR1 antagonism reversed post-stress escalation of alcohol drinking and reduced avoidance behavior in Avoiders. Collectively, these findings suggest that elucidation of the mechanisms by which CRFR1-gated CeA circuits regulate avoidance behavior and alcohol drinking may lead to better understanding of the neural mechanisms underlying co-morbid PTSD and AUD.

neuroscience↗