Cross-sensitization between cocaine and acute restraint stress is associated with sensitized dopamine but not glutamate release in the nucleus accumbens. Eur J Neurosci 2013 Mar;37(6):982-95
Date
01/31/2013Pubmed ID
23360446Pubmed Central ID
PMC4356180DOI
10.1111/ejn.12121Scopus ID
2-s2.0-84875366554 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Repeated administration of psychostimulant drugs or stress can elicit a sensitized response to the stimulating and reinforcing properties of the drug. Here we explore the mechanisms in the nucleus accumbens (NAc) whereby an acute restraint stress augments the acute locomotor response to cocaine. This was accomplished by a combination of behavioral pharmacology, microdialysis measures of extracellular dopamine and glutamate, and Western blotting for GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor (AMPAR). A single exposure to restraint stress 3 weeks before testing revealed that enduring locomotor sensitization to cocaine was paralleled by an increase in extracellular dopamine in the core, but not the shell subcompartment, of the NAc. Wistar rats pre-exposed to acute stress showed increased basal levels of glutamate in the core, but the increase in glutamate by acute cocaine was blunted. The alterations in extracellular glutamate seem to be relevant, as blocking AMPAR by 6-cyano-7-nitroquinoxaline-2,3-dione microinjection into the core prevented both the behavioral cross-sensitization and the augmented increase in cocaine-induced extracellular dopamine. Further implicating glutamate, the locomotor response to AMPAR stimulation in the core was potentiated, but not in the shell of pre-stressed animals, and this was accompanied by an increase in NAc GluR1 surface expression. This study provides evidence that the long-term expression of restraint stress-induced behavioral cross-sensitization to cocaine recapitulates some mechanisms thought to underpin the sensitization induced by daily cocaine administration, and shows that long-term neurobiological changes induced in the NAc by acute stress are consequential in the expression of cross-sensitization to cocaine.
Author List
Garcia-Keller C, Martinez SA, Esparza MA, Bollati F, Kalivas PW, Cancela LMAuthor
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
6-Cyano-7-nitroquinoxaline-2,3-dioneAnimals
Central Nervous System Sensitization
Central Nervous System Stimulants
Cocaine
Dopamine
Exocytosis
Gene Expression
Glutamic Acid
Locomotion
Male
Neurons
Nucleus Accumbens
Protein Transport
Rats
Rats, Wistar
Receptors, AMPA
Restraint, Physical
Stress, Psychological
