The role of the insular cortex in naloxone-induced conditioned place aversion in morphine-dependent mice

A negative emotional state resulting from the withdrawal of drug addiction is thought to be an important factor that triggers and exacerbates relapse. Since the insular cortex is a key brain structure involved in the modulation of negative emotions, we investigated whether the integrity of the insular cortex was important for motivational aversion associated with morphine withdrawal as well as whether this kind of negative emotion induced neuroadaptation in the insular cortex. In this present study, a sensitive mouse conditioned place aversion (CPA) model measuring the motivational aversion of morphine withdrawal was first established. Our results showed that bilateral insular cortex lesions by kainic acid completely inhibited the expression of CPA. The expression of FosB/deltaFosB in the insular cortex was significantly increased 24 h after the CPA regime was performed, but the expression of c-Fos in the insular cortex did not changed. These findings indicate that the integrity of the insular cortex is essential to motivational aversion associated with morphine withdrawal, and that this kind of aversion induces neuroadaptation, observed as the increase of FosB/deltaFosB expression, in the insular cortex.