ArticleTranslational psychiatry2018
A novel rat model of comorbid PTSD and addiction reveals intersections between stress susceptibility and enhanced cocaine seeking with a role for mGlu5 receptors.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Fear conditioning enhances subsequent cocaine self-administration and amygdala neuronal activity only in male rats.Neuropharmacology · 2026Article
- Stress-coping behavior during predator odor exposure is associated with differences in decision making.Addiction neuroscience · 2026Article
- Sex-dependent Schizophrenia and Drug Reward Behavioral Phenotypes in Metabotropic Glutamate 5 Receptor Heterozygous and Homozygous Mice.Schizophrenia bulletin · 2026Article
- Stress-coping behavior during predator odor exposure is associated with differences in decision making.bioRxiv : the preprint server for biology · 2026Article
- Threat Conditioning Prior to Cocaine or Sucrose Exposure Alters Reward-Seeking Behavior in a Sex-Dependent Manner.Psychiatry international · 2026Article
- The persistent effects of exposure to a predator odor stressor on sensitivity to alcohol.Addiction neuroscience · 2025Article
- Fatty acid amide hydrolase inhibition alleviates anxiety-like symptoms in a rat model used to study post-traumatic stress disorder.Psychopharmacology · 2025Article
- Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats.Addiction neuroscience · 2025Article
- Sex-specific effects of predator scent stress on fear, anxiety-like behavior and methamphetamine seeking in rats.Addiction neuroscience · 2025Article
- Crystallin Alpha B Inhibits Cocaine-Induced Conditioned Place Preference via the Modulation of Dopaminergic Neurotransmission.Addiction biology · 2025Article
- Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Sex-specific effects of chronic stress prior to cocaine exposure on cue- vs drug-induced relapse after prolonged abstinence.Behavioural brain research · 2024Article
- Predator odor stress reactivity, alcohol drinking and the endocannabinoid system.Neurobiology of stress · 2024Article
- Predator Odor Stressor, 2,3,5-Trimethyl-3-Thiazoline (TMT): Assessment of Stress Reactive Behaviors During an Animal Model of Traumatic Stress in Rats.Current protocols · 2024Article
- Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking.Scientific reports · 2023Article
- Sex-dependent fear memory impairment in cocaine-sired rat offspring.Science advances · 2023Article
- Role of mesolimbic cannabinoid receptor 1 in stress-driven increases in cocaine self-administration in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Brain Monoamine Dysfunction in Response to Predator Scent Stress Accompanies Stress-Susceptibility in Female Rats.Biomolecules · 2023Article
- Steady electrocorticogram characteristics predict specific stress-induced behavioral phenotypes.Frontiers in neuroscience · 2023Article
- Sex differences in cocaine self-administration by Wistar rats after predator odor exposure.Advances in drug and alcohol research · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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 2,5-dihydro-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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.