Long-term impact of acute restraint stress on heroin self-administration, reinstatement, and stress reactivity. Psychopharmacology (Berl) 2020 Jun;237(6):1709-1721
Date
03/04/2020Pubmed ID
32125483Pubmed Central ID
PMC7857092DOI
10.1007/s00213-020-05486-zScopus ID
2-s2.0-85081605223 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
RATIONALE: There is a robust relationship between anxiety disorders, including post-traumatic stress disorder (PTSD) and substance abuse. In fact, 30-50% of people seeking treatment for substance abuse have a comorbid diagnosis for PTSD. Heroin use is at epic proportions in the USA and is commonly used by people with co-occurring PTSD symptoms and substance use disorder.
OBJECTIVES: Here, we combined animal assays of acute restraint stress and contingent heroin self-administration (SA) to study comorbidity between stress disorders and opioid use disorder and identify shifts in anxiety-like behaviors following stress and/or heroin in response to a stress-conditioned cue. Our objective for this approach was to determine the long-term impact of acute restraint stress and heroin self-administration on stress reactivity and basic reward processes.
METHODS: We used 2-h acute restraint stress paired with an odor stimulus to condition a stress cue (CS) for testing of subsequent stress reactivity in a burying task and reinstatement and extinction to heroin seeking. Rats were also tested for social place preference for measures of social reward and anxiety-like behaviors.
RESULTS: Stress rats exhibited multiple levels of disrupted behavior including enhanced acquisition of heroin intake and reinstatement in response to the stress CS, as well as delayed extinction in response to the stress CS. All rats developed a social place preference, but stress rats spent more time in nose-to-nose contact with the unfamiliar rat while heroin rats spent time exploring the chamber. In the burying task, stress shortened latencies to bury the CS and increased burying and immobility in male and female rats relative to sham counterparts.
CONCLUSIONS: Acute restraint stress results in anxiety-like behaviors and a stress-associated cue is sufficient to reinstate extinguished heroin seeking. This project has the potential to elucidate the complex relationship between stress/anxiety disorders, including some PTSD-like characteristics, and the onset, maintenance, and relapse to heroin seeking.
Author List
Carter JS, Kearns AM, Vollmer KM, Garcia-Keller C, Weber RA, Baker NL, Kalivas PW, Reichel CMAuthor
Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCues
Extinction, Psychological
Female
Heroin
Heroin Dependence
Male
Odorants
Random Allocation
Rats
Rats, Sprague-Dawley
Restraint, Physical
Self Administration
Stress, Psychological
