Cocaine-induced disruptions of information flow from the basolateral amygdala to the insula

Understanding persistent dysregulations induced by chronic drug use on neuronal networks is crucial in order to develop appropriate therapeutic approach for addiction. The basolateral amygdala (BLA), involved in emotional processing, as well as the insular cortex (IC), involved in interoception, have been proposed to play a central role in cue-induced reinstatement of cocaine seeking behavior. In addition, functional imaging studies in abstinent users have shown an increased synchronization of the IC and the amygdala, which suggests dysfunction of this circuitry that could increase vulnerability to cues associated to drug use [1]. Our hypothesis is that chronic drug use induces long-lasting disruption of information processing within the amygdala-IC circuit. In particular, exposure to drug cues during abstinence, would activate this pathway and reactivate the representations of the drug’s interoceptive effects leading to intense craving and increasing the risk of relapse. The aim of the present study was to examine cocaine-induced persistent changes in i) spontaneous activity of the BLA and the IC and ii) synaptic plasticity in the BLA-IC pathway. To test this hypothesis, we first allowed rats to self-administer cocaine for 10 days (6 h/day; FR1 schedule; 0.15 mg/injection). Control “yoked” received an injection of saline, each time the paired “master” rat self-administered an injection of cocaine. After a 30-day abstinence period, we performed in vivo single-unit extracellular recordings in anesthetized rats to measure spontaneous activity of the BLA and the IC. We then studied BLA-evoked IC local field potentials (eLFPs) after theta burst electrical stimulation (six trains of 100 pulses at 100 Hz, 20s between trains), that is known to induce an LTP of IC response in control animals, and low frequency electrical stimulation (5 Hz, 200 sec), that is known to induce a depotentiation of IC response, to the BLA. Two-way ANOVAs have been performed for behavioral and synaptic plasticity data and a Mann-Whitney test has been used for spontaneous activity analysis. We found that self-administration of cocaine produces a significant increase in the bursting activity (saline: 23.8% of spikes in bursts, n=35; cocaine: 41.01% spikes in bursts, n = 43; p