Abstract
Background
Posttraumatic stress disorder (PTSD) co-occurs with substance use disorders at high
rates, but the neurobiological basis of this relationship is largely unknown. PTSD
and drug addiction each involve dysregulation of brain reward circuitry; therefore,
the identification of pathology of the mesolimbic dopamine system may aid in understanding
their functional relationship. Dopamine reward dysfunction also may be relevant to
the mechanisms underlying the PTSD symptoms of anhedonia and emotional numbing.
Methods
Single-prolonged stress (SPS) was used as a rat model of PTSD, and a series of behavioral
and neuropharmacologic assays were applied to assess the impact of SPS on reward,
cocaine intake, and components of the striatal dopamine system.
Results
Exposure to SPS increased anhedonia-like behaviors and decreased the rewarding properties
of cocaine compared with control handling. Altered cocaine intake during extended
access self-administration sessions was observed in rats exposed to SPS, further suggesting
a difference in the reinforcing properties of cocaine following severe stress. SPS
reduced tissue content of dopamine and its metabolites in the striatum, as well as
altered striatal dopamine transporter and D2, but not D1, receptor densities.
Conclusions
These results support a role for altered dopaminergic transmission in reduced reward
function in PTSD. Pathology of the dopamine system and the degradation of reward processes
may contribute to PTSD symptomology and have implications for co-occurring psychiatric
disorders such as substance abuse or depression.
Keywords
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Article info
Publication history
Published online: May 05, 2015
Accepted:
April 29,
2015
Received in revised form:
April 10,
2015
Received:
November 4,
2014
Identification
Copyright
© 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Capturing Individual Differences: Challenges in Animal Models of Posttraumatic Stress Disorder and Drug AbuseBiological PsychiatryVol. 78Issue 12
- PreviewMany psychiatric disorders are comorbid with substance use disorder (SUD). Individuals with any mood or anxiety disorder are twice as likely to develop SUD compared with healthy individuals (1). Patients with posttraumatic stress disorder (PTSD) are no exception, with PTSD patients four times more likely to develop SUD than individuals without PTSD (2). However, despite numerous clinical reports of increased drug use in patients with PTSD and other mood disorders, preclinical studies have had difficulty replicating these effects in rodents.
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