Browsing by Author "Houck, Christa A."

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    Acute drug effects on habitual and non-habitual responding in crossed high alcohol preferring mice
    (Springer Nature, 2018-07) Houck, Christa A.; Grahame, Nicholas J.; Psychology, School of Science
    RATIONALE: Drug reward plays a central role in acquiring drug-seeking behavior. However, subjects may continue using drugs despite negative consequences because self-administration becomes habitual, and divorced from outcome values. Although a history of drug and alcohol use expedite habit acquisition, and in spite of the fact that self-administration leads to intoxication, the acute effects of drugs on habitual responding are not well understood. OBJECTIVES: We sought to observe how acute ethanol and amphetamine affect the balance between habitual and goal-directed behavior, as measured by a fluid-reinforced operant conditioning task. METHODS: Selectively bred crossed high-alcohol-preferring (cHAP) mice were trained on an operant conditioning task reinforced on a variable interval schedule with 1% banana solution, which was subsequently devalued via LiCl pairing in half the animals. Ethanol (1.0 g/kg), amphetamine (2.0 mg/kg), or saline was administered prior to a post-devaluation test. RESULTS: Overall, mice showed habitual behavior, but when divided into high- or low-responding groups based on training response rates, saline-treated, low-responding animals devalued, while saline-treated high-responding animals did not. Furthermore, amphetamine elicited devaluation even in high-responding animals, while ethanol prevented devaluation even in low-responding animals. CONCLUSIONS: These data show that ethanol shifts animals toward behaving habitually. This may illuminate why alcohol-intoxicated individuals display impaired judgment about the relative merits of drinking, and potentially serve as a mechanism by which intoxicated subjects resume previously devalued behaviors, such as comorbid drug use. These findings also show that high variable interval response rates facilitate a shift from goal-directed to habitual behavior.
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    Blockade of Striatal Dopamine D1 Receptors Reduces Quinine-Resistant Alcohol Intake
    (2019-05) Houck, Christa A.; Grahame, Nicholas J.; Boehm, Stephen L.; Logrip, Marian L.; Hopf, F. Woodward
    Drinking despite aversive consequences, or compulsive drinking, is a criterion of alcohol use disorder and can be modeled in rodents by adding bitter quinine into alcohol. Previous studies have shown the development of quinine-resistant ethanol (EtOH) drinking following a drinking history, but used animals that achieved relatively low blood alcohol levels. Selectively bred crossed High Alcohol Preferring (cHAP) mice average over 250 mg/dl during a two-bottle choice procedure. Compulsive drinking is hypothesized to be D1-receptor mediated via the dorsolateral striatum (DLS). We hypothesized that 2 weeks of free-choice EtOH would lead to quinine resistance and intra-DLS infusion of a D1-antagonist, SCH23390, would attenuate quinine-resistant alcohol drinking with no effect on non-conflicted EtOH drinking. Infusion of SCH23390 into the DMS would not affect quinine-resistant drinking. cHAP mice had guide cannulae placed in the DLS or DMS and had either two weeks (2W) of EtOH and water two-bottle choice or were EtOH naïve (0W). Mice were infused with either SCH23390 or saline immediately prior to one 10% EtOH and water test day and SCH23390 did not disturb alcohol drinking. The following day, we adulterated the EtOH with 0.32-g/L quinine (0.89 mM), and mice received the same microinjection. For animals cannulated in the DLS, 2W history group infused with saline drank more quinine-adulterated EtOH than the 0W saline mice. While SCH23390 infused 0W animals looked no different from saline treated mice, it attenuated quinine + EtOH intake in the 2W animals to the level of 0W animals. Interestingly, DMS-cannulated mice demonstrated similar behavior, with SCH23390 reducing EtOH + quinine consumption, while leaving EtOH consumption undisturbed. Quinine resistance following 2 weeks of free-choice EtOH consumption is attenuated by acute administration of a D1-antagonist in the DLS, suggesting that an alcohol history induces compulsivity and that dopamine contributes to this behavior. This is unique to compulsive drinking, as non-conflicted EtOH drinking was unaffected.
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    Innate and Acquired Quinine‐Resistant Alcohol, but not Saccharin, Drinking in Crossed High–Alcohol‐Preferring Mice
    (Wiley, 2019-11) Houck, Christa A.; Carron, Claire R.; Millie, Lauren A.; Grahame, Nicholas J.; Psychology, School of Science
    Background Alcohol consumption despite aversive consequences is often a key component of an alcoholism diagnosis. Free‐choice alcohol consumption despite bitter quinine adulteration in rodents has been seen following several months of free‐choice drinking, but there has been little study of whether prolonged access to other palatable substances such as saccharin yields quinine resistance. Selectively bred crossed high–alcohol‐preferring (cHAP) mice average blood alcohol levels of over 250 mg/dl during free‐choice access, considerably higher than other models. We hypothesized that higher intakes would yield more rapid development of quinine‐resistant alcohol (QRA) drinking and quinine‐resistant saccharin (QRS) drinking. Methods All experiments used male and female cHAP mice. Experiment 1 compared mice with either 0 or 5 weeks of alcohol drinking history, testing varying (0.032, 0.10, 0.32 g/l) quinine concentrations in ethanol. Experiment 2 examined whether innate QR may exist, comparing animals with a 1 or zero day of drinking history. Experiment 3 examined the effect of varying histories (0, 2, or 5 weeks) of free‐choice 10% alcohol drinking on QR alcohol consumption at high quinine concentrations. Finally, Experiment 4 investigated the development of QRS drinking. Results We found that we could not detect a history effect in commonly used quinine concentrations, indicating that cHAP mice are innately quinine resistant to 0.10 g/l quinine. However, we were able to determine that a 2‐week drinking history was sufficient to induce QRA drinking in cHAP mice at extremely high quinine concentrations (0.74 and 0.32 g/l). However, the history effect was specific to QRA, a saccharin drinking history, did not yield QRS drinking. Conclusions These data suggest that an alcohol drinking history induces maladaptive behaviors, such as drinking in spite of negative consequences, a pattern not seen with saccharin. Furthermore, a strong genetic predisposition to drink may promote an innate aversion resistance compared with commonly used inbred strains.
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    Pharmacological Modulation of Habit Expression
    (2016-08-17) Houck, Christa A.; Grahame, Nicholas J.; Czachowski, Cristine Lynn; Goodlett, Charles R.
    Habit expression is emerging as a theory of addiction: subjects begin to use drugs to attain positive reinforcing effects but continue to use in spite of negative effects because the behavior becomes habitual, and therefore divorced from its outcome. Many studies have shown that a history of drug and alcohol use lead to expedited acquisition of a habit, but the acute effects of these drugs on behavior is still unknown. Behaviors that result from acute intoxication, such as increased aggression, risky sexual behavior, and impaired judgment, could be interpreted as habitual: actions performed without regard for the outcome. Therefore, we studied the transition from goal-directed to habitual behavior, when a response is made regardless of outcome value, and how acute intoxication of ethanol (EtOH), amphetamine (AMP), nicotine (NIC), and yohimbine (YOH) affect the resulting behavior. Through a series of four experiments, selectively bred crossed High Alcohol Preferring (cHAP) mice were trained on an operant task to self-administer 1% banana solution, which was subsequently devalued via LiCl CTA. EtOH (1 & 1.5 g/kg), AMP (2.0 mg/kg), NIC (0.5 mg/kg), YOH (1.0 mg/kg), or SAL were administered prior to baseline and post-devaluation tests. We found that acute EtOH at 1- and 1.5-g/kg doses facilitated the expression of a habit, whereas all other pretreatments resulted in devaluation. These data may indicate a unique role for EtOH in facilitating the retrieval of habitual over outcome-based associations. This could shed light on why intoxicated individuals display impaired judgment and a mechanism by which relapse after a period of abstinence can occur.