Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats
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Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective.
The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation.
Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol (BM)) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e., non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in experiment 2 received vehicle or BM into the AI after a 15-min reexposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later.
BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine memory reconsolidation.
These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.
KeywordsMemory reconsolidation Context Cocaine seeking Agranular insular cortex Self-administration Baclofen muscimol Reinstatement
This work was supported by NIDA grants R01 DA017673 and DA025646.
Compliance with ethical standards
All protocols for the housing and treatment of animals were approved by the Institutional Animal Care and Use Committee and followed the Guide for the Care and Use of Laboratory Rats (Institute of Laboratory Animal Resources on Life Sciences 2011).
Conflict of interest
The authors declare that they have no conflicts of interest.
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