Biology subjects

Bluitt, M. N.

Publications and source records attributed to Bluitt, M. N..

5 recordsLinked to original sources

bioRxiv2025

Individual differences in punished alcohol self-administration are unaltered by alcohol vapor exposure

Continued alcohol use despite negative consequences is a defining feature of alcohol use disorder (AUD). It remains poorly understood whether individual variability in drinking despite negative consequences is due to inherent differences or emerges after prolonged alcohol use. The goal of the present study was to use a rat model of drinking despite negative consequences to assess individual differences in foot shock-punished alcohol self-administration prior to and following alcohol vapor exposure in male Wistar rats. After baseline operant self-administration was established, rats underwent additional self-administration sessions in which random, response-contingent foot shock punishment was introduced. Average percent change from baseline was calculated for each rat during punished sessions and rats were classified into shock-sensitive (SS) and shock-resistant (SR) subgroups using the top and bottom thirds. Rats then underwent 3 cycles of air or alcohol vapor exposure every other week, with unpunished self-administration sessions occurring during the intervening weeks. Following the last vapor cycle, rats were re-assessed for resistance to foot shock during punished self-administration sessions. Alcohol vapor exposure had no effect on punished self-administration overall, nor by subgroup. Examination of individual differences showed that rats classified as SR showed increased unpunished self-administration relative to baseline regardless of air vs. vapor condition. These data suggest that alcohol history has a minimal effect on individual differences in foot shock-punished self-administration.

animal behavior and cognition↗

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↗

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↗

bioRxiv2022

Enhanced food motivation in obese mice is controlled by D1R expressing spiny projection neurons in the nucleus accumbens.

Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and motivation are altered in obese animals. Here, we tested the hypothesis that signaling through pro-motivational circuits in the core of the nucleus accumbens (NAc) is enhanced in the obese state, leading to invigoration of food seeking. Using a novel behavioral assay that quantifies physical work during food seeking, we confirmed that obese mice work harder than lean mice to obtain food, consistent with an increase in the relative reinforcing value of food in the obese state. To explain this behavioral finding, we recorded neural activity in the NAc core with both in vivo electrophysiology and cell-type specific calcium fiber photometry. Here we observed greater activation of D1-receptor expressing NAc spiny projection neurons (NAc D1SPNs) during food seeking in obese mice relative to lean mice. With ex vivo slice physiology we identified both pre- and post-synaptic mechanisms that contribute to this enhancement in NAc D1SPN activity in obese mice. Finally, blocking synaptic transmission from D1SPNs decreased physical work during food seeking and attenuated high-fat diet-induced weight gain. These experiments demonstrate that obesity is associated with a selective increase in the activity of D1SPNs during food seeking, which enhances the vigor of food seeking. This work also establishes the necessity of D1SPNs in the development of diet-induced obesity, establishing these neurons as a potential therapeutic target for preventing obesity.

neuroscience↗

bioRxiv2021

The effects of predator odor (TMT) exposure and mGlu3 NAM pretreatment on lasting behavioral and molecular adaptations in the insular cortex and BNST

A stressor can trigger adaptations that contribute to neuropsychiatric disorders. Predator odor (TMT) exposure is an innate stressor that produces lasting adaptations. TMT exposure may activate metabotropic glutamate receptor 3 (mGlu3), triggering excitatory corticolimbic adaptations that underlie behavioral changes. To evaluate functional involvement, the mGlu3 negative allosteric modulator (NAM, VU6010572; 3 mg/kg, i.p.) was administered before TMT exposure in male, Long Evans rats. Two weeks after stressor, rats underwent behavioral testing (context re-exposure, zero maze and acoustic startle response) followed by RT-PCR gene expression in the insular cortex and BNST. During the TMT exposure, rats displayed stress-reactive behaviors that were not affected by the VU6010572. During the context re-exposure, prior TMT exposure and VU6010572 pretreatment both produced a hyperactive response. TMT exposure did not affect zero maze or ASR measures, but VU6010572 increased time spent in the open arms and habituation to ASR, indicating anxiolytic-like effects. In the insular cortex, TMT exposure resulted in excitatory adaptations as shown by increased expression of mGlu (Grm3, Grm5), NMDA (GriN2A, GriN2B, GriN2C, GriN3A, GriN3B) and AMPA (GriA3) receptor transcripts. Interestingly, mGlu3 signaling during stressor mediated GriN3B upregulation. Stress reactivity during TMT exposure was associated with Grm5, GriN2A, GriN2C, and GriA3 upregulation in the insular cortex and context re-exposure reactivity in the TMT/vehicle, but not the TMT/mGlu3 NAM group. In the BNST, GriN2A, GriN2B and GriN3B were increased by VU6010572, but TMT prevented these effects. These data demonstrate that mGlu3 signaling contributes to the lasting behavioral and molecular adaptations of predator odor stressor.

neuroscience↗