Effects of inactivating the agranular or granular insular cortex on the acquisition of the morphine-induced conditioned place preference and naloxone-precipitated conditioned place aversion in rats.

Recent studies have indicated that the insula underlies affective learning. Although affective learning is well-established in the development of opiate addiction, the role of insula in this context remains unclear. To elucidate the organization of opiate-related affective learning within the insular cortex, we reversibly inactivated each of two major subdivisions of the insula in rats and tested the effects of this inactivation on the acquisition of morphine-induced conditioned place preference (CPP) and conditioned place aversion (CPA) induced by naloxone-precipitated acute morphine withdrawal. Results showed that inactivation of the primary interoceptive posterior granular insula (GI), but not that of the high-order anterior agranular insula (AI), disrupted the acquisition of CPP and that both GI and AI inactivation impaired the acquisition of CPA. These data suggest that the insular cortex is involved in positive and negative affective learning related to opiate addiction. In particular, the GI appears to be critical for both forms of affective learning, whereas the AI is crucial for learning associated with negative affects induced by opiate withdrawal.