EFECTO DE LA ADMINISTRACIÓN REPETIDA DE COCAÍNA SOBRE LA MODULACIÓN DOPAMINÉRGICA D2 EN NUCLEO ACCUMBENS CORE

PEREZ, M.F.

Los Andes, Chile

Conferencia; Sociedad de Neurociencia Chilena; 2007

Sociedad de Neurociencia Chilena

The nucleus accumbens (NAc) is a limbic structure in the brain, which plays a critical role in cognition and addiction. Repeated cocaine exposure alters dopamine (DA) transmission and decreases voltage-sensitive Ca2+ influx in medium spiny neurons (MSNs) in the NAc. Though DA D1-like receptor (D1R)-mediated signaling is enhanced, it is unknown whether and how D1-like receptor (D2R) is implicated in cocaine-induced NAc dysfunction. Here, we performed a combined electrophysiological, biochemical, and neuroimaging study that reveals cocaine-induced dysregulation of Ca2+ homeostasis modulated by D2R. Our novel findings indicate that D2R stimulation suppressed Ca2+ influx via L-type Ca2+ channels, but evoked intracellular Ca2+ release with inhibition of cAMP/PKA cascade in NAc MSNs of drug-free rats. However, repeated cocaine exposure enhanced PKA activity and abolished D2R effects on modulating Ca2+ influx and release. These adaptations, which were region-specific and persisted for 3 weeks during abstinence, may contribute to the mechanism of cocaine withdrawal.