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Browsing by Subject "Alcohol-preferring rat"

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    Changes in Gene Expression within the Ventral Tegmental Area Following Repeated Excessive Binge-Like Alcohol Drinking by Alcohol-Preferring (P) Rats
    (Elsevier, 2013) McBride, William J.; Kimpel, Mark W.; McClintick, Jeanette N.; Ding, Zheng-Ming; Hauser, Sheketha R.; Edenberg, Howard J.; Bell, Richard L.; Rodd, Zachary A.; Psychiatry, School of Medicine
    The objective of this study was to detect changes in gene expression in the ventral tegmental area (VTA) following repeated excessive binge-like ('loss-of-control') alcohol drinking by alcohol-preferring (P) rats. Adult female P rats (n = 7) were given concurrent access to 10, 20, and 30% EtOH for 4 1-h sessions daily for 10 weeks followed by 2 cycles of 2 weeks of abstinence and 2 weeks of EtOH access. Rats were sacrificed by decapitation 3 h after the 4th daily EtOH-access session at the end of the second 2-week relapse period. A water-control group of female P rats (n = 8) was also sacrificed. RNA was prepared from micro-punch samples of the VTA from individual rats; analyses were conducted with Affymetrix Rat 230.2 GeneChips. Ethanol intakes were 1.2-1.7 g/kg per session, resulting in blood levels >200 mg% at the end of the 4th session. There were 211 unique named genes that significantly differed (FDR = 0.1) between the water and EtOH groups. Bioinformatics analyses indicated alterations in a) transcription factors that reduced excitation-coupled transcription and promoted excitotoxic neuronal damage involving clusters of genes associated with Nfkbia, Fos, and Srebf1, b) genes that reduced cholesterol and fatty acid synthesis, and increased protein degradation, and c) genes involved in cell-to-cell interactions and regulation of the actin cytoskeleton. Among the named genes, there were 62 genes that showed differences between alcohol-naïve P and non-preferring (NP) rats, with 43 of the genes changing toward NP-like expression levels following excessive binge-like drinking in the P rats. These genes are involved in a pro-inflammatory response, and enhanced response to glucocorticoids and steroid hormones. Overall, the results of this study indicate that the repeated excessive binge-like alcohol drinking can change the expression of genes that may alter neuronal function in several ways, some of which may be deleterious.
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    Encoding of the Intent to Drink Alcohol by the Prefrontal Cortex Is Blunted in Rats with a Family History of Excessive Drinking
    (Society for Neuroscience, 2019) Lisenbardt, David N.; Timme, Nicholas M.; Lapish, Christopher C.; Psychology, School of Science
    The prefrontal cortex (PFC) plays a central role in guiding decision making, and its function is altered by alcohol use and an individual's innate risk for excessive alcohol drinking. The primary goal of this work was to determine how neural activity in the PFC guides the decision to drink. Towards this goal, the within-session changes in neural activity were measured from medial PFC (mPFC) of rats performing a drinking procedure that allowed them to consume or abstain from alcohol in a self-paced manner. Recordings were obtained from rats that either lacked or expressed an innate risk for excessive alcohol intake, Wistar or alcohol-preferring (P) rats, respectively. Wistar rats exhibited patterns of neural activity consistent with the intention to drink or abstain from drinking, whereas these patterns were blunted or absent in P rats. Collectively, these data indicate that neural activity patterns in mPFC associated with the intention to drink alcohol are influenced by innate risk for excessive alcohol drinking. This observation may indicate a lack of control over the decision to drink by this otherwise well-validated supervisory brain region.
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    Impulsivity in rodents with a genetic predisposition for excessive alcohol consumption is associated with a lack of a prospective strategy
    (Springer, 2017-04) Linsenbardt, David N.; Smoker, Michael P.; Janetsian-Fritz, Sarine S.; Lapish, Christopher C.; Psychology, School of Science
    Increasing evidence supports the hypothesis that impulsive decision-making is a heritable risk factor for an alcohol use disorder (AUD). Clearly identifying a link between impulsivity and AUD risk, however, is complicated by the fact that both AUDs and impulsivity are heterogeneous constructs. Understanding the link between the two requires identifying the underlying cognitive factors that lead to impulsive choices. Rodent models have established that a family history of excessive drinking can lead to the expression of a transgenerational impulsive phenotype, suggesting heritable alterations in the decision-making process. In the present study, we explored the cognitive processes underlying impulsive choice in a validated, selectively bred rodent model of excessive drinking-the alcohol-preferring ("P") rat. Impulsivity was measured via delay discounting (DD), and P rats exhibited an impulsive phenotype as compared to their outbred foundation strain-Wistar rats. Steeper discounting in P rats was associated with a lack of a prospective behavioral strategy, which was observed in Wistar rats and was directly related to DD. To further explore the underlying cognitive factors mediating these observations, a drift diffusion model of DD was constructed. These simulations supported the hypothesis that prospective memory of the delayed reward guided choice decisions, slowed discounting, and optimized the fit of the model to the experimental data. Collectively, these data suggest that a deficit in forming or maintaining a prospective behavioral plan is a critical intermediary to delaying reward, and by extension, may underlie the inability to delay reward in those with increased AUD risk.
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    An investigation of the neural circuitry of cued alcohol behaviors in P and Wistar rats
    (2017-12) McCane, Aqilah Maryam; Lapish, Christopher; Czachowski, Cristine
    Alcohol-paired cues invigorate alcohol-seeking and drinking behaviors in both rodents and individuals with alcohol use disorder (AUD). Additionally, genetic susceptibility plays a key role in alcohol addiction behaviors. Alcohol preferring (P) rats model both genetic vulnerability and symptoms of AUD. The basolateral amygdala (BLA), prefrontal cortex (PFC), hippocampus (HC) and nucleus accumbens (NA) are important brain regions involved in cued alcohol seeking. These regions are interconnected and their functional connections are hypothesized to be critical in the expression of motivated behaviors. Electrophysiological recordings in these four regions were collected in P rats engaged in a cued alcohol task. Data were filtered in the theta band (5-11 Hz) and segregated by behavioral epoch. The phase locking index γ was computed and used to measure strength of phase locking between signals from any two brain regions. The cross correlation between the amplitude of two signals was used to determine directionality. PFC-NA synchrony increased after stimuli presentation and remained elevated, relative to baseline synchrony. PFC-NA synchrony was also stronger for trials in which the animal made three or more lever presses (rewarded; R), compared to trials in which the animal responded fewer than three times (not-rewarded; NR). During lever pressing, PFC-BLA, NA-HC and PFC-HC synchrony was stronger after presentation of the DS+, in R compared to NR trials. NA-HC and PFC-BLA synchrony was stronger when responses were withheld in extinction, relative to conditioning. These data inform our knowledge of how corticolimbic connections are involved in cued ethanol seeking behaviors.
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