UC San Diego

Prior research has implicated interoceptive processing in the insular cortex as a critical component in drug craving. The goal of this thesis was to elucidate the role the insular cortex plays in the experience of the direct rewarding effects of drugs, as measured by brain stimulation. Neuronal activity was inhibited by infusion of the local anesthetic bupivacaine into the rostral insular cortex (RI) or the caudal insular cortex (CI) prior to testing rats in an intracranial self-stimulation (ICSS) paradigm to measure brain reward current intensity thresholds. Rats received either an injection of d- amphetamine (0.5 mg/kg) or saline vehicle 5 min after bupivacaine infusions. Inactivation of the RI but not CI elevated brain reward thresholds in amphetamine-naïve rats , suggesting the rostral insula with its interconnections with reward circuitry may modulate the experience of reward from brain stimulation. Inactivation of the RI or CI with infusions volumes that were inactive in amphetamine-naive rats did not alter the reward-enhancing effects of 0.5 mg/kg d-amphetamine, suggesting that this dose of d-amphetamine produces its reward-enhancing effects independent of its interoceptive effects which are integrated by the insula