Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats.
Psychopharmacology (Berl). 2017 Aug; 234(16):2431-2441.P

Abstract

RATIONALE

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.

OBJECTIVES

The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation.

METHODS

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.

RESULTS

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.

CONCLUSIONS

These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.

Links

Publisher Full Text
ncbi.nlm.nih.gov
dx.doi.org
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Authors+Show Affiliations

Arguello AA
Department of Psychology, Michigan State University, East Lansing, MI, 48824, USA. Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA, 99164-7620, USA.
Wang R
Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA, 99164-7620, USA.
Lyons CM
Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA, 99164-7620, USA.
Higginbotham JA
Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA, 99164-7620, USA.
Hodges MA
Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA, 99164-7620, USA.
Fuchs RA
Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA, 99164-7620, USA. ritafuchs@vetmed.wsu.edu.

MeSH

AnimalsBaclofenCerebral CortexCocaineDopamine Plasma Membrane Transport ProteinsDrug-Seeking BehaviorExtinction, PsychologicalGABA AgonistsMaleMemoryMemory ConsolidationMuscimolRatsRats, Sprague-DawleySelf Administration

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28462472