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 brai n regions that contribute to its rewarding effects by allowing rats to self -administer cocaine (0.33 mg/infusion) for Ih a day for 1 month. Control an imals 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 proc essed for Golgi-Cox staining. In rats that self-administered cocaine, but n ot rats that worked for food, there was a significant increase in dendritic branching and in the density of dendritic spines on medium spiny neurons i n the shell of the nucleus accumbens and on pyramidal cells in the prefront al and parietal (but not occipital) cortex. There was also a 2.6-fold incre ase in the incidence of spines with multiple heads (branched spines) on med ium spiny neurons. Finally, in the prefrontal cortex some of the apical den drites of pyramidal cells appeared misshaped, having large bulbous structur es on their terminal tips. We speculate that cocaine self-administration ex perience alters patterns of synaptic connectivity within limbocortical circ uitry that is thought to contribute to cocaine's incentive motivational eff ects and may have neuropathological effects in frontal areas involved in de cision making and judgment. Together, these two classes of drug-induced neu roadaptations may contribute to the development of addiction. (C) 2001 Wile y-Liss, Inc.