Dynamic Alterations of Rat Nucleus Accumbens Dendritic Spines over 2 Months of Abstinence from Extended-Access Cocaine Self-Administration.

Chronic cocaine exposure influences the density and morphology of dendritic spines on medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a critical brain region for cocaine craving. However, the relationship between spine plasticity and craving remains unclear. To study this relationship, we trained rats to self-administer cocaine using an extended-access regimen (6 h per day, 10 days); controls self-administered saline.

Surface expression of GABAA receptors in the rat nucleus accumbens is increased in early but not late withdrawal from extended-access cocaine self-administration.

It is well established that cocaine-induced changes in glutamate receptor expression in the nucleus accumbens (NAc) play a significant role in animal models of cocaine addiction. Far less is known about cocaine-induced changes in GABA transmission, despite its importance in regulating NAc output via local interneurons and medium spiny neuron (MSN) axon collaterals (GABA 'microcircuit'). Here we investigated whether GABAA receptor surface or total expression is altered following an extended-access cocaine self-administration regimen that produces a time-dependent intensification (incubation) of cue-induced cocaine craving in association with strengthening of AMPA receptor (AMPAR) transmission onto MSN.