Repeated Cocaine Exposure Decreases Dopamine D2-Like Receptor Modulation of Ca2+ Homeostasis in Rat Nucleus Accumbens Neurons

MARIELA F. PÉREZ.; KERSTIN A. FORD , IVAN GOUSSAKOV, GRACE E. STUTZMANN, XIU-TI HU

SYNAPSE

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2010 vol. 65 p. 168 - 168

0887-4476

he nucleus accumbens is a limbic structure in the forebrain which plays a critical rolein cognitive function and addiction. Dopamine modulates activity of medium spinyneurons in the nucleus accumbens. Both dopamine D1-like and D2-like receptors(including D1R or D1,5R, and D2R or D2,3,4R, respectively) are thought to play criticalroles in cocaine addiction. Our previous studies demonstrated that repeated cocaineexposure (which alters dopamine transmission) decreases excitability of nucleusaccumbens medium spiny neurons in cocaine-sensitized, withdrawn rats. Thisdecrease is characterized by a reduction in voltage-sensitive Na+ currents and highvoltage-activated Ca2+ currents, along with increased voltage-gated K+ currents. Thesechanges are associated with enhanced activity in the D1R/cAMP/PKA/proteinphosphatase 1 pathway and diminished calcineurin function. Though D1R-mediatedsignaling is enhanced by repeated cocaine exposure, little is known whether and howthe D2R is implicated in the