Escalation of alcohol intake is associated with regionally decreased insular cortex activity but not changes in taste quality

Abstract

Background Intermittent access to ethanol drives persistent escalation of intake and rapid transition from moderate to compulsive‐like drinking. Intermittent ethanol drinking may facilitate escalation of intake in part by altering aversion‐sensitive neural substrates, such as the insular cortex (IC), thus driving greater approach toward stimuli previously treated as aversive. Methods We conducted a series of experiments in rats to examine behavioral and neural responses associated with escalation of ethanol intake. First, taste reactivity analyses quantified the degree to which intermittent brief‐access ethanol exposure (BAEE) alters sensitivity to the aversive properties of ethanol. Next, we determined whether pharmacological IC inhibition facilitated ethanol escalation. Finally, given that the IC is primary gustatory cortex, we employed psychophysical paradigms to assess whether escalation of ethanol intake induced changes in ethanol taste. These paradigms measured changes in sensitivity to the intensity of ethanol taste and whether escalation in intake shifts the salient taste quality of ethanol by measuring the degree to which the taste of ethanol generalized to a sucrose‐like (“sweet”) or quinine‐like (“bitter”) percept. Results We found a near‐complete loss of aversive oromotor responses in ethanol‐exposed relative to ethanol‐naïve rats. Additionally, we observed significantly lower expression of ethanol‐induced c‐Fos expression in the posterior IC in exposed rats relative to naïve rats. Inhibition of the IC resulted in a modest, but statistically reliable increase in the acceptance of higher ethanol concentrations in naïve rats. Finally, we found no evidence of changes in the psychophysical assessment of the taste of ethanol in exposed, relative to naïve, rats. Conclusions Our results demonstrate that neural activity within the IC adapts following repeated presentations of ethanol in a manner that correlates with reduced sensitivity to the aversive hedonic properties of ethanol. These data help to establish that alterations in IC activity may be driving exposure‐induced escalations in ethanol intake.

Real-time activity of dynorphin-expressing neurons in mouse central amygdala during alcohol drinking

“…The study described used many orders of magnitude more concentrated sucrose (200 mM or 6.8%) than the current study. To capture whether the bitter taste component of alcohol is what produces the unique CeA Dyn activity, future studies should measure CeA Dyn activity during consumption of varying concentrations of quinine or, perhaps even more relevant, mixtures of sucrose and quinine that are proposed to better mimic the taste of alcohol (see Mukherjee et al 2023).…”