RESUMO
BACKGROUND: Sensitivity to the adverse post-ingestive effects of ethanol likely serves as a deterrent to initiate alcohol consumption early in drinking and later may contribute to efforts to remain abstinent. Administering ethanol to naïve rats prior to Pavlovian conditioning procedures elicits robust ethanol-conditioned taste and place avoidance (CTA; CPA) mediated by its subjective interoceptive properties. The insular cortex (IC) has been implicated as a region involved in mediating sensitivity to the interoceptive properties of ethanol. Here, we examined whether bilateral lesions of the IC affect the acquisition and expression of taste and place avoidance in ethanol-induced CTA and CPA paradigms. METHODS: Adult male and female Wistar rats received bilateral excitotoxic lesions (ibotenic acid; 20 mg/mL; 0.3 µL) of the IC prior to conditioning procedures. Subsequently, rats were conditioned to associate a novel taste stimulus (0.1% saccharin) and context with the effects of ethanol (1.0 g/kg) in a combined CTA/CPP procedure. Conditioning occurred over 8 alternating CS+/CS- days, followed by tests for expression of taste and place preferences. Data from IC-lesioned rats were compared with neurologically intact rats. RESULTS: Our findings revealed that neurologically intact rats showed a significantly stronger ethanol-induced CTA than IC-lesioned rats. There were no significant differences in total fluid intake when rats consumed water (CS-). As with CTA effects, intact rats showed a strong CPA, marked by a greater reduction in time spent on the drug-paired context, while IC-lesioned rats failed to display CPA to ethanol. CONCLUSION: These results indicate that proper IC functioning is necessary for responding to the adverse interoceptive properties of ethanol regardless of which Pavlovian paradigm is used to assess interoceptive responsivity to ethanol. Blunted IC functioning from chronic ethanol use may reduce interoceptive signaling specifically of ethanol's adverse effects thus contributing to increased alcohol use.
RESUMO
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.
