AMPA receptor trafficking in the dorsal striatum is critical for behavioral sensitization to cocaine in juvenile mice

Advances in understanding the neurobiology of addiction indicate that not only dopaminergic neurotransmissions but also glutamatergic neurotransmissions within the mesolimbic system play important roles. While the role for the nucleus accumbens (NAc) shell and core in addiction has been extensively studied, the function of the dorsal striatum is not clear. Here, we demonstrate that repeated cocaine injections cause increases in surface-expressed AMPA receptors in the dorsal striatum. The increased AMPAR expression is more robust in juvenile mice than in young adult mice. Furthermore, expression of the G1CT peptide, which prevents the delivery of AMPARs to the surface, attenuates the locomotor sensitization in juvenile mice. Our results strongly suggest that glutamatergic synaptic plasticity in the dorsal striatum may have an important role in behavioral sensitization to cocaine and that there may be different age-dependent control mechanisms.