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Inactivation of the insular cortex increases anxiety-like behavior in rats : relevance to drug abuse and interoception

Abstract

The insular cortex is an integral component of the interoceptive circuit, and is thought to be important in regulating changes in hedonic valuation of interoceptive information. In this thesis, direct insular cortex manipulation or "silencing" of both the Caudal Granular Insular Cortex (CGIC) and Rostral Agranular Insular Cortex (RAIC) was used to examine the role of the insula in the interoceptive circuit as it relates to regulation of behavior. Insular inactivation resulted in behavioral modifications consistent with an increased anxiety-like state in the 1) place conditioning, 2) elevated plus maze, and 3) acoustic startle paradigms. In the conditioned place aversion test, RAIC and CGIC surgically altered animals showed an innate bias for the darker compartment which was not present in intact rats. Testing in the elevated plus maze revealed a significant anxiety-like effect following insula inactivation on the behavioral measures of percent time, percent distance and number of entries in the open arms of the maze. Lastly, a trend for elevated startle magnitude was seen in RAIC and CGIC rats, although only CGIC rats receiving infusions showed significantly higher startle magnitude. These anxiety-like effects detected after insular manipulation in each of the three behavioral paradigms indicate that the insula plays an important role in the interoceptive circuit responsible for coordinating the integration of external and internal stimuli as a means to generate behavior responses appropriate to the current state of the body, and thus may indicate a role for the insula in regulating drug addiction, anxiety, and other related indications

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