Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex.

We studied the influence of cocaine use on the structure of neurons in brain regions that contribute to its rewarding effects by allowing rats to self-administer cocaine (0.33 mg/infusion) for 1 h a day for 1 month. Control animals were left undisturbed or allowed to work for food for the same period of time. After an additional 1 month drug-free period the brains were processed for Golgi-Cox staining. In rats that self-administered cocaine, but not rats that worked for food, there was a significant increase in dendritic branching and in the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens and on pyramidal cells in the prefrontal and parietal (but not occipital) cortex. There was also a 2.6-fold increase in the incidence of spines with multiple heads (branched spines) on medium spiny neurons. Finally, in the prefrontal cortex some of the apical dendrites of pyramidal cells appeared misshaped, having large bulbous structures on their terminal tips. We speculate that cocaine self-administration experience alters patterns of synaptic connectivity within limbocortical circuitry that is thought to contribute to cocaine's incentive motivational effects and may have neuropathological effects in frontal areas involved in decision making and judgment. Together, these two classes of drug-induced neuroadaptations may contribute to the development of addiction.