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

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