Extracellular fluctuations of dopamine and glutamate in the nucleus accumbens core and shell associated with lever-pressing during cocaine self-administration, extinction, and yoked cocaine administration.

Abstract

Dopamine and glutamate in the nucleus accumbens (NAS) are differentially implicated in cocaine-directed behavior. We sought to compare extracellular fluctuations of dopamine and glutamate in core and shell of NAS associated with operant responding during cocaine self-administration, extinction, and yoked cocaine administration. Rats were trained to lever-press for cocaine or saline under FR1 before undergoing microdialysis testing during cocaine self-administration, extinction, or yoked cocaine administration. Microdialysis samples were collected every 20 min and were analyzed for dopamine and glutamate with high-performance liquid chromatography. Rats actively lever-pressed during cocaine self-administration and extinction. However, lever-pressing was minimal during yoked cocaine administration in both cocaine-trained and saline-trained rats. Dopamine was elevated throughout cocaine self-administration and yoked cocaine administration. The extent of cocaine-evoked dopamine was greater in shell than in core, greater in cocaine-trained than in saline-trained rats, and greater during self-administration than during yoked administration. Dopamine was also elevated in core (first 60 min) and in shell (first 40 min) during extinction. Basal concentration of glutamate, but not dopamine, was lower in cocaine-trained than in saline-trained rats. In cocaine-trained rats, glutamate was elevated during cocaine self-administration and extinction but was depressed below baseline during yoked cocaine administration. The extent and direction of glutamate fluctuation was similar between core and shell. In saline-trained rats, glutamate was not affected by yoked cocaine. Distinct patterns of dopamine and glutamate fluctuations in core and shell appear to underlie characteristic patterns of lever-pressing associated with cocaine self-administration, extinction, and yoked cocaine administration.