Previous studies investigating the neurobiology underlying the reinstatement of drug-seeking behavior, an animal model of relapse in drug-addicted individuals, have pointed to the medial prefrontal cortex as a critical node in this circuitry. In contrast, significantly less work has examined how different regions in the lateral prefrontal cortex influence reinstatement. In particular, the insular cortex, a region within the lateral prefrontal cortex, has been implicated in craving and relapse. Functional imaging studies suggest that drug-associated cues activate the insular cortex in individuals addicted to a variety of different drugs. In addition, damage or inactivation of this region disrupts nicotine addiction in both humans and animals. However, despite the evidence suggesting a role for this region in addiction to other drugs, few studies have investigated how different subregions of the insular cortex regulate cocaine-seeking behavior, particularly in animal models that allow for more precise neurobiological investigations into the mechanisms underlying its role in relapse/reinstatement. Our own now-published findings indicate that inactivation of the dorsal agranular insular cortex (AId) attenuates cued reinstatement but has no effect on cocaine-prime reinstatement in rats. However, the circuitry mechanisms underlying the role of the AId in the reinstatement of cocaine seeking remain unknown. Therefore, the present proposal will investigate the projections from the AId to different downstream regions to determine their role in cued reinstatement. Male and female Sprague-Dawley rats will undergo cocaine self-administration, followed by extinction training, prior to undergoing cued reinstatement testing. The proposed aim will determine whether chemogenetically inactivating either the AId?nucleus accumbens core or AId?basolateral amygdala pathway reduces lever pressing during cued reinstatement. The findings from this proposal will be instrumental in elucidating the neural circuits by which the AId is regulating cocaine-seeking behaviors.

Public Health Relevance

Cocaine addiction remains a costly and debilitating disorder in large part due to the high relapse rates observed in individuals addicted to different drugs of abuse. As prior research has identified the insular cortex as a potential region of interest in developing addiction treatments, the proposed experiments will expand upon previous findings demonstrating a role for the insular cortex in cued reinstatement of cocaine seeking by investigating the neural circuitry underlying this region?s regulation of such behavior. The results from these studies will be critical for developing new treatments that target this region as part of the ongoing effort to reduce relapse among drug-addicted individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DA043364-01
Application #
9260193
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Babecki, Beth
Project Start
2017-02-10
Project End
2017-12-15
Budget Start
2017-02-10
Budget End
2017-12-15
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Iowa
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242