Project III: Stress Circuits and Sex Differences in Drug Seeking (Aston-Jones) There is growing evidence for a relationship between stress reactivity and substance use disorders that differ by gender. Brain norepinephrine (NE) and corticotropin releasing factor (CRF) systems are important in stress responses. Recent findings indicate a link between the sex/gender differences in drug abuse and these brain systems: LC-NE neurons in females are more responsive to stressors and to CRFI receptor activation than in males. In addition, oxytocin (OT) neurons are involved in reward processes, perhaps via interactions with NE and CRF, and may play a role in drug craving. In this project we will characterize the roles of these systems in sex/gender-specific drug seeking using behavioral pharmacology and Fos immunohistochemistry in rodent model of cocaine seeking. We hypothesize that sex differences in the CRF-NE system facilitate increased cocaine seeking in females;specifically, we propose that the stress of eariy abstinence increases CRF input to LC, and that the higher response of LC-NE neurons to CRF in females leads to greater cocaine seeking and more difficulty in maintaining abstinence. We will test these ideas by (i) determining the ability of beta adrenoceptor or CRFI receptor antagonists to attenuate cocaine seeking during early abstinence, (ii) identifying NE and CRF neurons that are Fos-activated during eariy cocaine abstinence, and (iii) determining if CRFI receptor antagonism within LC attenuates cocaine seeking during eariy abstinence. Findings here will inform Projects 1 and 4 about circuitry and neurotransmitters involved in drug seeking in their clinical subjects, and Project 2 about upstream circuits that may influence the peptide systems studied there.

Public Health Relevance

This project will define the roles of specific brain systems in sex/gender differences in the initiation of abstinence from cocaine abuse. Results of these studies will lead to more effective treatments for addiction' in both males and females.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
2P50DA016511-11
Application #
8366431
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Project Start
Project End
Budget Start
2012-08-15
Budget End
2013-07-31
Support Year
11
Fiscal Year
2012
Total Cost
$185,698
Indirect Cost
$63,636
Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Cason, Angie M; Kohtz, Amy; Aston-Jones, Gary (2016) Role of Corticotropin Releasing Factor 1 Signaling in Cocaine Seeking during Early Extinction in Female and Male Rats. PLoS One 11:e0158577
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