Description
The insular cortex has been implicated in the acquisition and maintenance of substance abuse disorders via regulation of an organism's responsiveness to drug-associated sensory cues. Neuroimaging studies have indicated a role for the insula in response to drugrelated stimuli and the experience of drug craving, conversely lesions to the insula have been shown to result in a reduction in craving and increased ability to abstain in addicted smokers. Insular inactivation in rodents disrupts conditioned preference for environments previously paired with amphetamine or nicotine and prevents/suppresses cue-induced reinstatement of drug seeking. These effects are believed to reflect a disruption in insula-mediated processing of interoceptive state information activated by drug-related cues. With regard to alcohol, the chemosensory cues accompanying its administration are among the most salient predictors of its postabsorptive effects, and may stimulate affective state information processed by the insula. Prior research in our lab has demonstrated that pharmacological inactivation of the visceral interoceptive insula suppresses chemosensory cue reactivity to ethanol. The aim of the current study was to examine differences in ethanol cue-elicited activation of the visceral insular cortex in subjects with and without a history of chronic ethanol exposure. Adult Wistar rats (n=12/group) initially received chronic exposure to 20% ethanol, 0.5% saccharin, or water alone (naive) for five weeks in an intermittent-access voluntary drinking paradigm. After completion of the chronic exposure phase, naive and experienced subjects consumed a fixed volume of their corresponding exposure stimulus and c-Fos expression within the visceral insula was measured 90 minutes after cue exposure. Significant levels of intake and preference for both ethanol and saccharin were observed during the chronic exposure phase. Analysis of stimulus-induced Fos expression revealed strong activation of the dorsal visceral insula by 20% ethanol in the alcohol naive group, while significantly reduced in alcoholexperienced subjects. Lower levels of visceral Fos expression were observed in both saccharin-naive and saccharin-experienced animals, but did not significantly differ from controls. These data demonstrate robust oral ethanol-elicited neuronal activity within the visceral region of the insular cortex in rodents, suggesting the insula may play an important role in processing of novelty/prior experience of ethanol-related stimuli.
