Cocaine-induced Changes in the Expression of NMDA Receptor Subunits

Abstract

: Cocaine use disorder is manifested by repeated cycles of drug seeking and drug taking. Cocaine exposure causes synaptic transmission in the brain to exhibit persistent changes, which are poorly understood, while the pharmacotherapy of this disease has not been determined. Multiple potential mechanisms have been indicated to be involved in the etiology of cocaine use disorder. The glutamatergic system, especially N-methyl-D-aspartate (NMDA) receptors, may play a role in several physiological processes (synaptic plasticity, learning and memory) and in the pathogenesis of cocaine use disorder. The composition of the NMDA receptor subunits changes after contingent and noncontingent cocaine administration and after drug abstinence in a region-specific and timedependent manner, as well as depending on the different protocols used for cocaine administration. Changes in the expression of NMDA receptor subunits may underlie the transition from cocaine abuse to dependence, as well as the transition from cocaine dependence to cocaine withdrawal. In this paper, we summarize the current knowledge regarding neuroadaptations within NMDA receptor subunits and scaffolding proteins observed following voluntary and passive cocaine intake, as well as the effects of NMDA receptor antagonists on cocaine-induced behavioral changes during cocaine seeking and relapse.