Faculty Collaboration Database

Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration. Mol Psychiatry 2016 Aug;21(8):1063-9

Date

01/30/2016

Pubmed ID

26821978

Pubmed Central ID

PMC4823171

DOI

10.1038/mp.2015.151

Scopus ID

2-s2.0-84979220561 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.

Author List

Garcia-Keller C, Kupchik YM, Gipson CD, Brown RM, Spencer S, Bollati F, Esparza MA, Roberts-Wolfe DJ, Heinsbroek JA, Bobadilla AC, Cancela LM, Kalivas PW

Author

Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Ceftriaxone
Central Nervous System Stimulants
Cocaine
Cocaine-Related Disorders
Comorbidity
Dendritic Spines
Excitatory Amino Acid Agents
Extinction, Psychological
Glutamic Acid
Male
Nucleus Accumbens
Rats
Rats, Sprague-Dawley
Self Administration
Stress, Psychological
Synapses