IU Indianapolis ScholarWorks :: Browsing by Author "Czachowski, Cristine"

Browsing by Author "Czachowski, Cristine"

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Adolescent and Adult Two-Bottle Choice Ethanol Drinking and Adult Impulsivity in Genetically Selected High-Alcohol Preferring Mice
(2012-09-20) O'Tousa, David Scott; Grahame, Nicholas J.; Czachowski, Cristine; Boehm II, Stephen L.
Abuse of alcohol during adolescence continues to be a problem, and it has been shown that earlier onset of drinking predicts increased alcohol abuse problems later in life. High levels of impulsivity have been demonstrated to be characteristic of alcoholics, and impulsivity has also been shown to predict later alcohol use in teenage subjects, showing that impulsivity may be an inherent underlying biological process that precedes the development of alcohol use disorders. These experiments examined adolescent drinking in a high-drinking, relatively impulsive mouse population, and assessed its effects on adult drinking and adult impulsivity. Experiment 1: Selectively bred High-Alcohol Preferring (HAP II) mice, which are shown to be highly impulsive, were given either alcohol (free choice access) or water only for two weeks during middle adolescence or adulthood. All mice were given free choice access to alcohol following 30 days without access, in adulthood. Experiment 2: Adolescent HAP II mice drank alcohol and water, or water alone, for two weeks, and were then trained to perform a delay discounting task as adults to measure impulsivity. In each experiment, effects of volitional ethanol consumption on later behavior were assessed. We expected adolescent alcohol exposure to increase subsequent drinking and impulsivity. Adolescent mice consumed significant quantities of ethanol, reaching average blood ethanol concentrations (BECs) of 142 mg/dl in Experiment 1 and 108 mg/dl in Experiment 2. Adult mice reached average BECs of 154 mg/dl in Experiment 2. Mice pre-exposed to alcohol in either adolescence or adulthood showed a transient increase in ethanol consumption, but we observed no differences in impulsivity in adult mice as a function of whether mice drank alcohol during adolescence. These findings indicate that HAP II mice drink intoxicating levels of alcohol during both adolescence and adulthood, and that this volitional intake has long-term effects on subsequent drinking behavior. Nonetheless, this profound exposure to alcohol during adolescence does not increase impulsivity in adulthood, indicating that long-term changes in drinking are mediated by mechanisms other than impulsivity. Importantly, this research demonstrates that the HAP II mouse is a good candidate for a model of heavy adolescent alcohol consumption.
ALTERATIONS IN THE SEEKING AND SELF-ADMINISTRATION OF ETHANOL AND ANXIETY-LIKE BEHAVIOR FOLLOWING EXPOSURE TO YOHIMBINE IN RATS SELECTIVELY BRED FOR HIGH ALCOHOL INTAKE
(2011-08-16) Bertholomey, Megan Lee; Grahame, Nicholas J.; Czachowski, Cristine; Stewart, Robert; Chester, Julia A.
Stress has been shown to contribute to alcohol drinking; however, inconsistencies in both the clinical and pre-clinical literature speak to the need for better paradigms to study this interaction. The present experiments compared animal models of the propensity to consume ethanol, the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) rat lines, in their response to yohimbine on ethanol seeking and self-administration and anxiety-like behavior. The P and HAD lines consume similar amounts of ethanol, yet differ in apparent motivation to drink ethanol, in anxiety-like behavior, and response to stress in alcohol drinking. Therefore, it was of interest to determine whether stress may differentially affect ethanol-motivated behaviors between the P and HAD lines. Acute administration of yohimbine, an α-2 adrenoreceptor antagonist that increases anxiety and activate stress systems, increased operant ethanol self-administration and reinstatement of ethanol seeking in P rats, and free-choice ethanol drinking in both P and HAD rats. However, acute yohimbine administration decreased ethanol drinking when given limited access in the home cage, an effect that was diminished by extending the pre-treatment interval or increasing the number of ethanol exposure sessions. Yohimbine did not alter appetitive responding during a non-reinforced trial, nor did yohimbine alter the acquisition of free-choice ethanol drinking. Exposure to alcohol deprivation resulted in modest increases in ethanol intake, but yohimbine did not potentiate this effect. While acute yohimbine administration increased anxiety-like behavior, prior experience with repeated yohimbine exposures or with repeated deprivation periods did not. P rats were shown to be more active and less anxious and to display greater responding during a non-reinforced trial than HAD rats. Taken together, the results of these experiments demonstrate that the timing of yohimbine exposure relative to ethanol access is a critical component to determining its effects on ethanol seeking and self-administration and anxiety-like behavior. Further investigation into the parameters under which stress alters the motivation to seek and consume ethanol between these selectively bred lines is warranted, and future work that incorporates therapeutic agents aimed at reducing stress reactivity and alcohol drinking could elucidate effective strategies in the treatment of alcoholism.
Assessing Motivational and Associative Learning Mechanisms Underlying Compulsive Drinking
(2021-08) Carron, Claire R.; Grahame, Nicholas; Czachowski, Cristine; Lapish, Christopher; Hopf, Fredric
Continued consumption of alcohol despite the knowledge of negative consequences is a hallmark of alcohol use disorder (AUD), yet much remains unknown about what motivates these behaviors. Compulsive drinking may require motivational resources that are not necessary when drinking in unchallenged conditions in order to counteract the addition of these negative consequences. Increased sensitivity to drug-paired stimuli via associative learning processes may provide this additional motivation. To evaluate if alcohol-paired stimuli enhance alcohol seeking, selectively bred crossed High Alcohol Preferring mice experienced Pavlovian conditioning procedures with an alcohol unconditioned stimulus. We hypothesized that after repeated pairings, alcohol cues would elicit seeking conditioned responses. Then, to determine if the motivation provided by these cues influenced responding, mice were trained to respond for alcohol and tested in the presence of alcohol cues. Finally, to test if alcohol-paired cues influence compulsive drinking, this same test was repeated with the addition of response-contingent footshock. We hypothesized the cue paired with alcohol would increase responding for alcohol in unchallenged conditions, but especially in challenged conditions, contributing to compulsivity. An auditory stimulus paired with alcohol did elicit enhanced seeking responses, but contrary to hypothesis, we observed no effect of these same cues on instrumental responding. To validate these findings, training and testing procedures must be optimized to ensure conditioning has properly occurred and compulsivity is being appropriately measured.
Characterization of Behavioral Profiles for Inbred P and NP and Congenic P.NP and NP.P Rats
(2012-08-27) Jensen, Meredith; Grahame, Nicholas J.; Stewart, Robert; Czachowski, Cristine; Roman, Erika
Alcoholism inheritance rates have been estimated as high as 60% in a human population. Many significant features of alcohol dependence have been replicated in rodent animal models of alcoholism, however not in totality. These animal models include inbred preferring (iP) and nonpreferring (iNP) rat types. Congenic rats have been engineered from the iP and iNP strains whereby a P congenic rat has in its genome a well-chosen chromosomal portion taken from an NP rat (P.NP) and, reciprocally, an NP congenic rat has acquired the analogous DNA from a P rat (NP.P). In this case, a quantitative trait locus (QTL) from chromosome 4 is the donor genetic material for the congenic rats. It is of great interest to further study this chromosome 4 QTL because it has been found to control a significant portion of ethanol consumption behavior in iP and iNP rats. This study aimed to behaviorally profile the iP, iNP and reciprocal congenic rats. As a result of the behavioral profiling of these genetically related groups, some conclusions could be made regarding which behaviors appear to be controlled by the chromosome 4 donor DNA.This study primarily utilized the Multivariate Concentric Square Field apparatus (MCSF) to characterize behavioral profiles for the inbred and congenic rats. The Open field (OF) and Elevated plus maze (EPM) supported this effort. The MCSF is valuable in that it allows for the animals to interact within an environment that has ethological value. The 12 different zones that make up the field are characterized by some functional quality in terms of type and duration of behavior performed, etc. The behavioral data is aggregated and finally represented in terms of five functional categories, the elements of the behavioral profile: general activity, exploratory activity, risk assessment, risk taking, and shelter seeking. The study hypotheses were shaped by prior research suggesting that iPs should display lower general activity and risk taking strategy than iNPs in the MCSF. Inbred Ps should be more active in the OF and spend more time in the center of the EPM. Generally, it is expected that the iP QTL confer behavioral phenotypes to the iNP strain that deviate toward a "P" behavioral phenotype and reciprocally, the iNP QTL confer behavioral phenotypes to the iP strain that deviate toward an "NP" behavioral phenotype. The results showed that iP rats performed more risk assessment and risk taking behavior and less shelter seeking and anxiety-like behavior than iNP rats. It followed that P.NP congenic rats significantly downgraded their risk assessment and risk taking behavior when compared to iP rats. This decrease can be attributed to the chromosome 4 QTL donated from the iNP breed. All together this study concludes that risk assessment and risk taking behavior in the iP rats is controlled by the same DNA region that, in part, determines voluntary intake of ethanol consumption. Further fine mapping of the QTL region should help in discovering if the same DNA sequences that influence ethanol intake also significantly influence risk behavior.
Chronic Ethanol Drinking by Alcohol-preferring Rats Increases the Sensitivity of the Mesolimbic Dopamine System to the Reinforcing and Stimulating Effects of Cocaine
(2013-08-20) Oster, Scott M.; Murphy, James M.; Rodd, Zachary A.; Goodlett, Charles R.; Kinzig, Kimberly P.; Czachowski, Cristine; Hazer, John
Alcohol and cocaine are commonly co-abused drugs, and those meeting criteria for both cocaine and alcohol use disorders experience more severe behavioral and health consequences than those with a single disorder. Chronic alcohol (ethanol) drinking increased the reinforcing and dopamine (DA) neuronal stimulating effects of ethanol within mesolimbic regions of the central nervous system (CNS) of alcohol-preferring (P) rats. The objectives of the current study were to determine if chronic continuous ethanol drinking produced: (1) alterations in the sensitivity of the nucleus accumbens shell (AcbSh) to the reinforcing effects of cocaine, (2) changes in the magnitude and time course of the local stimulating effects of cocaine on posterior ventral tegmental area (pVTA) DA neurons, and (3) a persistence of alterations in the stimulating effects of cocaine after a period of protracted abstinence. Female P rats received continuous, free-choice access to water and 15% v/v ethanol for at least 10 wk (continuous ethanol-drinking; CE) or access to water alone (ethanol-naïve; N). A third group of rats received the same period of ethanol access followed by 30 d of protracted abstinence from ethanol (ethanol-abstinent; Ab). CE and Ab rats consumed, on average, 6-7 g/kg/d of ethanol. Animals with a single cannula aimed at the AcbSh responded for injections of cocaine into the AcbSh during four initial operant sessions. Cocaine was not present in the self-infused solution for the subsequent three sessions, and cocaine access was restored during one final session. Animals with dual ipsilateral cannulae aimed at the AcbSh and the pVTA were injected with pulsed microinfusions of cocaine into the pVTA while DA content was collected for analysis through a microdialysis probe inserted into the AcbSh. During the initial four sessions, neither CE nor N rats self-infused artificial cerebrospinal fluid (aCSF) or 0.1 mM cocaine into the AcbSh. CE, but not N, rats self-administered 0.5 mM cocaine into the AcbSh, whereas both groups self-infused concentrations of 1.0, 2.0, 4.0, or 8.0 mM cocaine. When cocaine access was restored in Session 8, CE rats responded more on the active lever and obtained more infusions of 0.5, 1.0, 2.0, or 4.0 mM cocaine compared to N rats. Microinjection of aCSF into the pVTA did not alter AcbSh DA levels in N, CE, or Ab rats. Microinjections of 0.25 mM cocaine into the pVTA did not significantly alter AcbSh DA levels in N animals, moderately increased DA levels in CE rats, and greatly increased DA levels in Ab rats. Microinjections of 0.5 mM cocaine into the pVTA modestly increased AcbSh DA levels in N animals, robustly increased DA levels in CE rats, and did not significantly alter DA levels in Ab rats. Microinjections of 1.0 or 2.0 mM cocaine into the pVTA modestly increased AcbSh DA levels in N animals but decreased DA levels in CE and Ab rats. Overall, long-term continuous ethanol drinking by P rats enhanced both the reinforcing effects of cocaine within the AcbSh and the stimulatory and inhibitory effects of cocaine on pVTA DA neurons. Alterations in the stimulatory and inhibitory effects of cocaine on pVTA DA neurons were not only enduring, but also enhanced, following a period of protracted abstinence from ethanol exposure. Translationally, prevention of chronic and excessive alcohol intake in populations with a genetic risk for substance abuse may reduce the likelihood of subsequent cocaine use.
De-Mixing Decision Representations in Rodent dmPFC to Investigate Strategy Change During Delay Discounting
(2023-05) White, Shelby M.; Lapish, Christopher; Czachowski, Cristine; Oberlin, Brandon; Seamans, Jeremy
Several pathological disorders are characterized by maladaptive decision-making (Dalley & Robbins, 2017). Decision-making tasks, such as Delay Discounting (DD), are used to assess the behavioral manifestations of maladaptive decision-making in both clinical and preclinical settings (de Wit, Flory, Acheson, Mccloskey, & Manuck, 2007). DD measures cognitive impulsivity and broadly refers to the inability to delay gratification (Hamilton et al., 2015). How decisions are made in tasks that measure DD can be understood by assessing patterns of behavior that are observable in the sequences of choices or the statistics that accompany each choice (e.g. response latency). These measures have led to insights that suggest strategies that are used by the agent to facilitate the decision (Linsenbardt, Smoker, Janetsian-Fritz, & Lapish, 2016). The current set of analyses aims to use individual trial data to identify the neural underpinnings associated with strategy transition during DD. A greater understanding of how strategy change occurs at a neural level will be useful for developing cognitive and behavioral strategies aimed at reducing impulsive choice. The rat dorso-medial prefrontal cortex (dmPFC) has been implicated as an important brain region for recognizing the need to change strategy during DD (Powell & Redish, 2016). Using advanced statistical techniques, such as demixed principal component analysis (dPCA), we can then begin to understand how decision representations evolve over the decision- making process to impact behaviors such as strategy change. This study was the first known attempt at using dPCA applied to individual sessions to accurately model how decision representations evolve across individual trials. Evidence exists that representations follow a breakdown and remapping at the individual trial level (Karlsson, Tervo, & Karpova, 2012; Powell & Redish, 2016). Furthermore, these representational changes across individual trials have previously been proposed to act as a signal to change strategies (Powell & Redish, 2016). This study aimed to test the hypothesis that a ‘breakdown’ followed by a ‘remapping’ of the decision representation would act as a signal to change strategy that is observable in the behavior of the animal. To investigate the relationship between trials surrounding the breakdown and/or subsequent remapping of the decision representation and trials surrounding strategy changes, sequences of trials surrounding the breakdown and/or remapping were compared to sequences of 9 trials surrounding the strategy-change trial. Strategy types consisted of either exploiting the immediate lever (IM-Exploit), delay lever (DEL-Exploit), or exploring between the two lever options (Explore). Contrary to the hypothesis, an overall relationship between breakdown and remapping trial sequences were not associated with change-trial sequences. In partial support of the hypothesis however, at the 4-sec delay when the subjective value of the immediate reward was high, a relationship between breakdown sequence and strategy change sequence was detected for when the animal was exploiting the delay lever (e.g. DEL-Exploit strategy). This result suggests that a breakdown in decision representation may act as a signal to prompt strategy change under certain contexts. One notable finding of this study was that the decision representation was much more robust at the 4-sec delay compared to the 8-sec delay, suggesting that decisions at the 4-sec delay contain more context that differentiate the two choice options (immediate or delay). In other words, the encoding of the two choice options was more dissociable at the 4-sec delay compared to the 8-sec delay, which was quantified by measuring the average distance between the two representations (immediate and delay) on a given trial. Given that Wistar rats are equally likely to choose between the immediate and delay choice alternatives at the 8-sec delay (Linsenbardt et al., 2016), this finding provides further support for current prevalent theories of how animals use a cognitive search process to mentally imagine choice alternatives during deliberation. If context which differentiates choice options at the 8-sec delay is less dissociable, it is likely that the cognitive search process would be equally likely to find either choice option. If the choice options are equally likely to be found, it would be assumed that the choice alternatives would also be equally likely to be chosen, which is what has been observed in Wistar rats at the 8-sec delay.
Does binge drinking induce PMDD-like dysfunction for female C57BL/6J mice? : implications for sex differences in addiction vulnerability
(2014) Melón, Laverne C.; Boehm, Stephen; Czachowski, Cristine; Grahame, Nicholas J.; Swithers, Susan E.
It has traditionally been posited that women show a "telescoped" development of alcohol use disorders (Kuhn, 2011). In particular, a number of clinical studies support striking sex differences in the progression from initial use of alcohol to dependence on the compound; with women showing a faster progression through landmark events associated with the development of alcohol addiction (Randall et al., 1999). However, recent studies have challenged this tenet (Keyes et al., 2010). The work presented herein was designed to determine whether females are indeed more vulnerable to the development of behavioral maladaptations following binge drinking and whether sex differences in GABA(A) receptor regulation might underlie this vulnerability. Using a mouse model of binge drinking this dissertation established that, compared to males, females escalate their binge drinking at a faster rate and maintain altered responsivity to the locomotor effects of alcohol after extended abstinence from binge drinking. Female mice also displayed significant increases in ethanol preference and intake in a continuous, two-bottle choice protocol following a shorter history of binge drinking than males. The final goal was to determine if binge drinking results in unique patterns of anxiety- or depressive-like symptoms in males and females and whether these behaviors would be associated with the dimorphic regulation of GABAA receptor subunits across the prefrontal cortex and hippocampus. Male binge drinkers displayed anxiety-like behavior during early withdrawal that dissipated after 2 weeks of abstinence. There were no significant changes in the expression of delta or gamma2 GABAA receptor subunit mRNA at this time point in the regions analyzed. Females also showed temporary anxiety-like behavior during early withdrawal from binge drinking. Additionally, females displayed significant depressive-like behavior after 2 weeks of abstinence from binge drinking. In particular, diestrus-phase females displayed significantly greater immobility in the forced-swim test after ethanol exposure and no longer maintained the reduced swim-time behavior associated with this phase of the cycle at baseline (when compared to the estrus-phase). qPCR analysis of hippocampal tissues from diestrus females supported a significant reduction in expression of gamma2 GABA(A) subunit mRNA after binge drinking. This effect was not noted for RNA isolated from hippocampal tissues taken during the estrus phase of bingers. These final data suggest possible interaction of estrous-cycle and binge drinking history that may result in the unique expression of deficits following binge drinking for females. Taken together, this work supports sex and estrous dependent effects of binge drinking on behavior and gene regulation.
Drinking Rhythms in Alcohol Preferring Mice
(2012-08-29) Matson, Liana M.; Grahame, Nicholas J.; Czachowski, Cristine; Boehm II, Stephen L.
Multiple lines of High Alcohol Preferring (HAP) mice were selectively bred for their intake of 10% ethanol (v/v) during 24-h daily access over a four-week period, with the highest drinking lines exhibiting intakes in excess of 20 g/kg/day. Drinking rhythms and corresponding blood ethanol concentrations (BEC) of the highest drinking HAP lines to those of the C57BL/6J (B6) inbred strain. Adult male and female crossed HAP (cHAP), HAP1 and B6 mice had free-choice access to 10% ethanol and water for 3 weeks prior to bi-hourly assessments of intake throughout the dark portion of a reverse 12:12 light dark cycle. In another cohort of cHAP mice, the same procedure was used to assess bi-hourly ethanol intake, and blood samples were taken across the day to look at the pattern of accumulation in these mice. Finally, considering the high level of intake by cHAP mice, we were interested in assessing whether metabolic and functional tolerance develop following chronic free-choice access, which were assessed using 2.0 and 1.75 g/kg challenge doses of 20% ethanol, respectively. cHAP and HAP1 mice maintained an excessive level of intake throughout the dark portion of the cycle, accumulating mean BEC levels of 261.5 + 18.09 and 217.9 + 25.02 mg/dl at 7-8 hours following lights off, respectively. B6 mice drank comparatively modestly, and did not accumulate high BEC levels (53.63 + 8.15 mg/dl). In the cHAP cohort, mean BECs were 112.47 + 19.91 at 2 hours after lights off, 189.00 + 27.40 at 6 hours after lights off, 193.80 + 29.66 at 10 hours after lights off, and 89.68 + 22.19 at 2 hours after lights on. Further, following 3 weeks of ethanol access, cHAP mice had a faster rate of ethanol metabolism and fewer hind slips than water-only exposed mice (ps < .05). In conclusion, the excessive free-choice drinking demonstrated by the HAP1 and cHAP lines, as well as the pattern of sustained high BECs in cHAP mice, challenge the notion that rodents will not reliably and voluntarily sustain ethanol intake at pharmacologically relevant levels. These results suggest that the highest drinking HAP lines may provide a unique opportunity for modeling the excessive intake that has been observed in alcohol-dependent individuals. Further, we observed that cHAP mice develop both metabolic and functional tolerance to the ataxic effects of ethanol following 3 weeks of free-choice access. Together, these findings support HAP mice as translational rodent model of alcoholism, and provide rationale for exploration of the predisposing factors for excessive consumption, as well as the development of physiological, behavioral, and toxicological outcomes following alcohol exposure.
Effects of acute and repeated cannabinoid injections on immediate and delayed object memory and unconditioned anxiety – a developmental trajectory
(2017-05) Kasten, Chelsea; Boehm II, Stephen L.; Czachowski, Cristine; Neal-Beliveau, Bethany; Powley, Terry
Cannabinoid receptors (CBRs) are inhibitory G-protein coupled receptors (GPCRs) that bind endogenous and exogenous cannabinoids. In an unaltered state, endogenous cannabinoids regulate system function and synchrony. Administration of cannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are found in the cannabis plant, can lead to disruptions in well-maintained inhibitory signaling. Although marijuana usage rates have been relatively stable since 2002, the number of young adolescents and adults that report perceiving marijuana as a “no risk” drug has doubled to more than 17% in each age group (Azofeifa et al., 2016). However, no drug is fully without risks. Preclinical studies have indicated that a history of THC during adolescence, but not adulthood, results in object memory impairments following a period of no-drug administration. In tests of unconditioned anxiety, acute THC evokes anxiety-like activity at higher doses. Conversely, CBD blocks object memory impairment in models that produce inflammation and also produces anxiolytic activity. Although THC and CBD are often used together for recreational and medical purposes, no study has observed the acute and long-lasting effects of THC+CBD in a battery of tests. The current work sought to fulfill three specific aims of research to identify both age and sex differences in response to cannabinoids. In Aim 1, a dose-response to acute THC or CBD was assessed in male and female adolescent and adult mice on the elevated plus maze (EPM) and open field (OF) activity. In Aim 2, acute vehicle, 10 mg/kg THC, 20 mg/kg CBD, and THC+CBD were assessed for their effects on memory consolidation, EPM, and OF activity in male and female mice during adolescence or adulthood. Mice from Aim 2 received a total of 8 injections over a 3 week period, then were given 3 weeks of rest. In Aim 3, all mice were tested again for object memory, EPM, and OF activity under no-drug conditions to assess the effects of an adolescent or adult history of cannabinoids in male and female mice. Results of Aim 1 indicated that adult mice, regardless of sex, were more sensitive to the acute effects of THC on unconditioned anxiety and locomotor activity. A rapid tolerance to THC may develop, as mice tested on the EPM in Aim 2 following their second injection of THC did not demonstrate anxiety-like activity that was present in Aim 1. However, anxiety-like activity persisted in the open field, and acute administration of THC+CBD resulted in synergistic effects on anxiety in adult females over THC alone. Interestingly, acute THC in adolescent males rescued a deficit in object memory in the vehicle group, whereas only adult males receiving vehicle showed significant object discrimination. Females were relatively resistant to effects of acute cannabinoids on object memory, with adolescents being completely insensitive. Results of Aim 3 indicated minimal effects of a history of cannabinoids on behavior. In contrast to previous experiments, an adolescent history of THC did not impair object memory. Interestingly, females administered THC+CBD during adulthood demonstrated impaired object memory following a no-drug period. Although CBD is often considered to lack a psychoactive profile, it is hypothesized that this impairment may be due to actions of CBD on 5HT1a receptors and require a fully-developed stress and gonadal system. The current results indicate that acute cannabinoid administration results in anxiety-like behavior when administered during adulthood, and that an adult history of THC+CBD in females results in impaired cognitive behavior. As the effects of cannabinoids were primarily present in adults, this may suggest that the fully-developed brain is more susceptible to interruption by acute and repeated exogenous cannabinoid administration and that adolescents may have a higher threshold for impairment of behavior.
Evaluating Sex and Line Differences in Successive Negative Contrast and Ethanol Consumption Using Alcohol Preferring and High Alcohol Drinking Rats
(2023-12) Smith, Nicholle; Czachowski, Cristine; Grahame, Nicholas; Logrip, Marian
A loss of a job or relationship are a few examples of unexpected reward loss. Life events such as these can induce negative emotional reactions (e.g., anxiety and stress) which have been associated with increased drinking and in turn, an increased risk of developing an alcohol use disorder (AUD) (Keyes et al., 2011, Sinha, 2008). The present study used a consummatory successive negative contrast (SNC) procedure to demonstrate unexpected reward loss reactivity in two lines selectively bred to consume high amounts of ethanol, alcohol preferring (P) and high alcohol drinking (HAD) rats. Following this reward loss, animals were given free access to ethanol to determine if ethanol consumption would increase to negate any negative emotional reaction provoked by this loss. P rats demonstrated a longer contrast effect than HAD rats, indicated by a longer recovery time following the downshift in reward. Conversely, HAD males did not demonstrate a contrast effect following this downshift in reward. Surprisingly, P rats who experienced a loss of reward consumed significantly less ethanol than animals who did not. Lastly, an individual measure of contrast size, or shift ratio, was significantly associated with greater ethanol consumption in HAD males only, who did not display a contrast effect. These data indicate different reactivity to SNC between these two lines and sexes, suggesting different genetic and sex-related mechanisms underlying sensitivity to an unexpected loss of reward.

Browsing by Author "Czachowski, Cristine"

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