Journal article
A novel rat model of comorbid PTSD and addiction reveals intersections between stress susceptibility and enhanced cocaine seeking with a role for mGlu5 receptors
Translational psychiatry, v 8(1), pp 209-14
05 Oct 2018
PMID: 30291225
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
PTSD is highly comorbid with cocaine use disorder (CUD), and cocaine users with PTSD + CUD are more resistant to treatment. Here we sought to develop a rat model of PTSD + CUD in order to identify the neurobiological changes underlying such comorbidity and screen potential medications for reducing cocaine seeking in the PTSD population. We utilized a predator scent stress model of PTSD, wherein rats received a single exposure to the fox pheromone 2,5dihydro-2,4,5-trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible (susceptible), intermediate, and resilient phenotypes were detected and were consistent with behavioral, corticosterone, and gene expression profiles 3 weeks post TMT. We assessed phenotypic differences in cocaine self-administration, extinction, and cue-primed reinstatement. Susceptible rats exhibited deficits in extinction learning and increased cue-primed reinstatement that was not prevented by Ceftriaxone, an antibiotic that consistently attenuates the reinstatement of cocaine seeking. TMT-exposed resilient rats displayed increased mGlu5 gene expression in the amygdala and medial prefrontal cortex and did not display the enhanced cocaine seeking observed in susceptible rats. Combined treatment with the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1 H-pyrazol-5-yl)benzamide (CDPPB), fear extinction, and ceftriaxone prevented the reinstatement of cocaine seeking in susceptible rats with fear extinction an important mediating condition. These results highlight the need for animal models of PTSD to consider stress-responsivity, as only a subset of trauma-exposed individuals develop PTSD and these individuals likely exhibit distinct neurobiological changes compared with trauma-exposed populations who are resilient to stress. This work further identifies glutamate homeostasis and mGlu5 as a target for treating relapse in comorbid PTSD-cocaine addiction.
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Details
- Title
- A novel rat model of comorbid PTSD and addiction reveals intersections between stress susceptibility and enhanced cocaine seeking with a role for mGlu5 receptors
- Creators
- Marek Schwendt - University of FloridaJohn Shallcross - University of FloridaNatalie A. Hadad - University of FloridaMark D. Namba - University of FloridaHelmut Hiller - University of FloridaLizhen Wu - University of FloridaEric G. Krause - University of FloridaLori A. Knackstedt - University of Florida
- Publication Details
- Translational psychiatry, v 8(1), pp 209-14
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- 8738sc; 9250sc / Institute on Molecular Neuroscience DA033436 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000446657800001
- Scopus ID
- 2-s2.0-85054442620
- Other Identifier
- 991021955787904721
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- Web of Science research areas
- Psychiatry