Crossed high alcohol preferring mice exhibit aversion-resistant responding for alcohol with quinine but not footshock punishment - PubMed (original) (raw)

Crossed high alcohol preferring mice exhibit aversion-resistant responding for alcohol with quinine but not footshock punishment

Elizabeth A Sneddon et al. Alcohol. 2022 Dec.

Abstract

A symptom of alcohol use disorder (AUD) is compulsive drinking, or drinking that persists despite negative consequences. In mice, aversion-resistant models are used to model compulsive-like drinking by pairing the response for alcohol with a footshock or by adding quinine, a bitter tastant, to the alcohol solution. crossed High Alcohol Preferring (cHAP) mice, a selectively bred line of mice that consumes pharmacologically relevant levels of alcohol, demonstrate a high level of aversion-resistance to quinine-adulterated alcohol. The current study investigated quinine-resistant and footshock-resistant responding for 10% ethanol in male and female cHAP mice with vs. without a history of alcohol exposure. cHAP mice were first trained to respond for 10% ethanol in an operant-response task. Next, mice were exposed to water or 10% ethanol for twelve 24-h sessions using a two-bottle choice procedure. Footshock-resistant ethanol responding was then tested in the operant chamber by pairing a footshock (0.35 mA) with the nose-poke response during one session. Quinine-resistant responding for alcohol was tested over five sessions (500-2500 μM quinine). Finally, footshock sensitivity was assessed using a flinch, jump, vocalize test. Alcohol exposure history did not influence responses for 10% ethanol or either measure of aversion-resistance. Further, cHAP mice were sensitive to footshock punishment but continued to respond for alcohol at all quinine concentrations. No sex differences were observed in any measure of alcohol responding, but female cHAP mice were less sensitive to footshock than males. These results replicate and extend the previous demonstration of a robust, innate resistance to quinine aversion in cHAP mice and further suggest that this tendency is not observed when footshock is used to punish drinking.

Keywords: alcohol; aversion-resistant; crossed high alcohol preferring; footshock; operant; quinine.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicting interests in this work.

Figures

Fig. 1.. Male and female cHAP mice consume similar amounts of ethanol and exhibit aversion-resistant responding for ethanol paired with quinine.

Mice had access to either 10% ethanol and water or two bottles of water alone for twelve 24-h sessions. A) Timeline of operant training. Mice participated in one day of autoshaping, one day responding for food, four days responding for 10% sucrose + 10% ethanol, and then seven total days responding for 10% ethanol. Two weeks elapsed and then mice drank in the 24-h continuous access paradigm. Following home cage drinking, mice were food-restricted for nine days and then operant testing with a footshock commenced. Mice responded for 10% ethanol for five days and were then shocked at 0.35 mA the following day. Mice were kept on food restriction and were tested on the operant testing phase with quinine seven days later. Mice responded to 10% ethanol for three days, and then quinine was added to the ethanol solution in escalating concentrations (500, 750, 1000, 1500, 2500 μM). Each quinine concentration was only presented once. B) Home cage consumption and C) preference for ethanol escalated over time in male and female cHAP mice. D) Water consumption in ethanol-drinking mice and E) water-drinking mice varied over time. F) Male mice respond more for 10% ethanol regardless of ethanol exposure history. G) Male and female cHAP mice reduced active responding when punished with a 0.35-mA footshock, regardless of ethanol exposure history. H) Responding on the inactive nose-poke hole was not influenced by drinking history, sex, or footshock punishment. I) cHAP mice did not reduce responding on the active nose-poke hole when quinine was added to the ethanol solution, regardless of ethanol drinking history. J) Male cHAP mice responded more on the inactive nose-poke hole than female mice during quinine sessions. *p < 0.05, **p < 0.01 (three-way ANOVA). #p < 0.05, ##p < 0.01, ###p < 0.001 (Dunnett’s vs. session 1 or Holm-Sidak’s vs. 10% ethanol (Testing).

Fig. 2.. Reduced sensitivity to footshock in female cHAP mice.

A) Footshock sensitivity was tested with a flinch, jump, vocalize procedure five days following the last operant testing session with quinine. Mice were shocked in increasing amplitudes from 0.05 to 0.95 mA (1 s). B) Sensitivity to footshock was lower in female mice across responses. **p < 0.01 (three-way ANOVA).

References

1. Almeida OFX, Shoaib M, Deicke J, Fischer D, Darwish MH, & Patchev VK (1998). Gender differences in ethanol preference and ingestion in rats. The Journal of Clinical Investigation, 101(12), 2677–2685. - PMC - PubMed
1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
1. Amodeo LR, Wills DN, Sanchez-Alavez M, Nguyen W, Conti B, & Ehlers CL (2018). Intermittent voluntary ethanol consumption combined with ethanol vapor exposure during adolescence increases drinking and alters other behaviors in adulthood in female and male rats. Alcohol, 73, 57–66. - PMC - PubMed
1. Barrot M (2012). Tests and models of nociception and pain in rodents. Neuroscience, 211, 39–50. - PubMed
1. Bauer MR, McVey MM, & Boehm SL 2nd. (2021). Three weeks of binge alcohol drinking generates increased alcohol front-loading and robust compulsive-like alcohol drinking in male and female C57BL/6J mice. Alcoholism: Clinical and Experimental Research, 45(3), 650–660. - PMC - PubMed

Crossed high alcohol preferring mice exhibit aversion-resistant responding for alcohol with quinine but not footshock punishment - PubMed (original) (raw)