Biology subjects

Henricks, A. M.

Publications and source records attributed to Henricks, A. M..

6 recordsLinked to original sources

bioRxiv2025

Prenatal anti-oxidant treatment suppresses maternal immune activation induced increases in alcohol self-administration in a sex-specific manner

Prenatal exposure to infection is a risk factor in the development of several neuropsychiatric disorders, including schizophrenia and depression, which often co-occur with alcohol misuse, exacerbating adverse outcomes. Despite these consequences, little is understood regarding the mechanisms by which early exposure to infection might increase the risk of alcohol misuse. We have previously demonstrated that maternal immune activation (MIA) combined with adolescent alcohol exposure (AA) increases home-cage drinking and disrupts neural circuit function in adulthood. The current project aims to determine whether these findings extend to the motivation to work for alcohol, and whether prenatal anti-oxidant treatment can prevent the effects of MIA on self-administration. Pregnant Sprague-Dawley rats were exposed to poly(I:C) (4mg/kg) or saline on gestational day 15, and the anti-oxidant n-acetylcysteine (NAC; 100 mg/kg) or saline 24 hours before and after MIA. Offspring were given 24-hour home cage access to 10% ethanol and water dur adolescence. In adulthood, offspring were trained to self-administer 10% ethanol and tested on escalating schedules of reinforcement: fixed ratio (FR)1, FR2, FR4, and progressive ratios (PR). MIA and NAC independently led to an increased willingness to work for alcohol in males, compared to saline-treated rats. NAC treatment suppressed the effect of MIA on self-administration behavior. These data support the hypothesis that oxidative stress caused by MIA negatively influences development, priming the brain to be more susceptible to the negative effects of AA, leading to an increased risk of alcohol misuse in adulthood, particularly in males.

pharmacology and toxicology↗

bioRxiv2024

Chronic intermittent alcohol yields sex-specific disruptions in cortical-striatal-limbic oscillations

BackgroundWhile the neurobiology of alcohol use disorder (AUD) has been extensively researched, the vast majority of these studies included only male organisms. However, there are significant sex differences in both the causes and consequences of alcohol misuse and dependence, suggesting sex-specific neurobiological mechanisms. The current study used a rodent model to determine whether chronic alcohol exposure impacts sex-specific neural circuits, and whether these changes contribute to the development of alcohol misuse. MethodsMale and female Sprague-Dawley rats were trained to self-administer 10% alcohol before implanting bilateral electrodes into the infralimbic medial prefrontal cortex (IL), nucleus accumbens shell (NAcSh), and central nucleus of the amygdala (CeA). Half of the rats were then exposed to four weeks of chronic intermittent alcohol (CIA) vapor (14 hours on/10 hours off). During acute withdrawal (6-8 after the vapor turns off), local field potentials (LFPs) were recorded from the IL, NAcSh, and CeA during 30-minute self-administration sessions. Using an unbiased machine learning approach, we built predictive models to determine whether/which LFP features could distinguish CIA-exposed from control rats in each sex, as well as if any of these LFP features correlated with rates of alcohol self-administration. ResultsFemale rats self-administered more alcohol in general compared to males, but only males exposed to CIA showed increased alcohol intake during acute withdrawal. LFPs predicted CIA exposure in both sexes better than chance estimates, but models built on IL and NAcSh oscillations performed the best in males, while models built on IL and CeA LFPs performed best in females. High {gamma} LFPs recorded in the NAcSh correlated with rates of alcohol self-administration in males exposed to CIA, while only left-right NAcSh {beta} coherence correlated with drinking in control females. ConclusionsThese data provide support for the hypothesis that the neural circuits driving alcohol dependence development are sex-specific, and that high frequency oscillations in the NAcSh may be related to the increased drinking observed in males exposed to CIA. Overall, these data add to our understanding of the neurobiological underpinnings behind the sex differences observed in AUD and offer promising biomarkers for future therapeutic research.

neuroscience↗

bioRxiv2022

Psychedelics enhance the effects of brain stimulation in rodents

BackgroundPsychedelic drugs have resurged in neuroscience and psychiatry with promising success in psychedelic-assisted therapy for the treatment of anxiety, depression, and addiction. At the cellular level, psychedelic drugs elicit neuroplastic processes 24 hours after administration, priming neural circuits for change. The acute effects of psychedelic drugs are well characterized with functional imaging and neural oscillations showing an increase in the entropy of spontaneous cortical activity. HypothesesWe hypothesized that cortical-striatal oscillations recorded in rats would confirm the effects of psychedelic drugs. We also hypothesized that brain stimulation delivered 24 hours after LSD administration would lead to different effects than brain stimulation alone. MethodsWe recorded local field potential (LFP) oscillations from rats following lysergic acid diethylamide (LSD) or saline administration and determined if exposure to these treatments altered the effect of a targeted intervention (brain stimulation) 24 hours later. ResultsWe confirmed acutely decreased low frequency power across the brain when rats are given LSD. We also demonstrated these altered states return to baseline after 24 hours. Brain stimulation applied in the previously reported window of heightened neuroplasticity produced distinct shifts in brain state compared to brain stimulation applied 24 hours after saline. ConclusionsDespite the acute effects of LSD disappearing after 24 hours, there are still latent effects that interact with brain stimulation to create larger and distinct changes in brain activity compared to brain stimulation alone. Our proof-of-concept findings are the first to suggest that psychedelic drugs could work in combination with brain stimulation to achieve enhanced effects on brain activity and future work will assess impacts on stimulation induced changes in behavior.

neuroscience↗

bioRxiv2022

Maternal immune activation and adolescent alcohol exposure increases alcohol drinking and disrupts cortical-striatal-hippocampal oscillations in adult offspring

Maternal immune activation (MIA) is strongly associated with an increased risk of developing mental illness in adulthood, which often co-occurs with alcohol misuse. The current study aimed to begin to determine whether MIA, combined with adolescent alcohol exposure (AE), could be used as a model with which we could study the neurobiological mechanisms behind such co-occurring disorders. Pregnant Sprague-Dawley rats were treated with PolyI:C or saline on gestational day 15. Half of the offspring were given continuous access to alcohol during adolescence, leading to four experimental groups: controls, MIA, AE, and Dual (MIA + AE). We then evaluated whether MIA and/or AE alters: 1) alcohol consumption; and 2) cortical-striatal-hippocampal oscillations in adult offspring. Dual rats, particularly females, drank significantly more alcohol in adulthood compared to all other groups. Using machine learning to build predictive models from oscillations, we were able to differentiate Dual rats from control rats and AE rats in both sexes, and Dual rats from MIA rats in females. The current data suggest that MIA+AE (Dual "hits") is a valuable model that we can use to study the neurobiological underpinnings of co-occurring disorders. Our future work aims to extend these findings to other addictive substances to enhance the translational relevance of this model.

neuroscience↗

bioRxiv2019

Sex differences in the ability of corticostriatal oscillations to predict rodent alcohol consumption

BackgroundAlthough male and female rats differ in their patterns of alcohol use, little is known regarding the neural circuit activity that underlies these differences in behavior. The current study used a machine learning approach to characterize sex differences in local field potential (LFP) oscillations that may relate to sex differences in alcohol drinking behavior.\n\nMethodsLFP oscillations were recorded from the nucleus accumbens shell and the rodent medial prefrontal cortex of adult male and female Sprague-Dawley rats. Recordings occurred before rats were exposed to alcohol (n=10/sex X 2 recordings/rat) and during sessions of limited access to alcohol (n=5/sex X 5 recordings/rat). Oscillations were also recorded from each female rat in each phase of estrous prior to alcohol exposure. Using machine-learning, we built predictive models to classify rats based on: 1) biological sex; 2) phase of estrous; and 3) alcohol intake levels. We evaluated model performance from real data by comparing it to the performance of models built and tested on permutations of the data.\n\nResultsOur data demonstrate that corticostriatal oscillations were able to predict alcohol intake levels in males (p<0.01), but not in females (p=0.45). The accuracies of models predicting biological sex and phase of estrous were related to fluctuations observed in alcohol drinking levels; females in diestrus drank more alcohol than males (p=0.052), and the male vs. diestrus female model had the highest accuracy (71.01%) compared to chance estimates.\n\nConversely, females in estrus drank similar amounts of alcohol to males (p=0.702), and the male vs. estrus female model had the lowest accuracy (56.14%) compared to chance estimates.\n\nConclusionsThe current data demonstrate that oscillations recorded from corticostriatal circuits contain significant information regarding alcohol drinking in males, but not alcohol drinking in females. Future work will focus on identifying where to record LFP oscillations in order to predict alcohol drinking in females, which may help elucidate sex-specific neural targets for future therapeutic development.

neuroscience↗

bioRxiv2018

Identifying neural predictors of response to cortical or striatal deep brain stimulation in a rodent model of alcohol drinking: Towards developing individualized therapies for alcohol use disorders

Individuals differ in their vulnerability to develop alcohol dependence that are determined by innate and environmental factors. The corticostriatal circuit is heavily involved in the development of alcohol dependence and may contain neural information regarding vulnerability to drink excessively. In the current experiment, we hypothesized that we could characterize high and low alcohol-drinking rats (HD and LD, respectively) based on corticostriatal oscillations, and that these subgroups would differentially respond to corticostriatal brain stimulation. Rats were trained to drink 10% alcohol in a limited access paradigm. In separate sessions, local field potentials (LFPs) were recorded from the nucleus accumbens shell (NAcSh) and medial prefrontal cortex (mPFC) of male Sprague-Dawley rats (n=13). Based on training alcohol consumption levels, we classified rats using a median split as HD or LD. Then, using machine-learning, we built predictive models to classify rats as HD or LD by corticostriatal LFPs and compared the model performance from real data to the performance of models built on data permutations. Additionally, we explored the impact of NAcSh or mPFC stimulation on alcohol consumption in HD vs. LD. Corticostriatal LFPs were able predict HD vs. LD group classification with greater accuracy than expected by chance (>80% accuracy). Additionally, NAcSh stimulation significantly reduced alcohol consumption in HD, but not LD (p<0.05), while mPFC stimulation did not alter drinking behavior in either HD or LD (p>0.05). These data collectively show that the corticostriatal circuit is differentially involved in regulating alcohol intake in HD vs. LD rats, and suggests that corticostriatal activity may have the potential to predict a vulnerability to develop alcohol dependence in a clinical population.

neuroscience↗