[Introduction] Methamphetamine (METH) is one of the most widely addictive drugs in the world. Repeated drug use frequently leads to cognitive impairment, but no effective treatment has been established. In the presents study, we examined the cognitive function of mice with injection of METH to the nucleus accumbens (NAc) to clarify the mechanism of cognitive impairment induced by METH.

[Method] C57BL/6J mice (8-week-old, male) received administration of METH via implanted cannula in the NAc for seven consecutive  days. Behavioral experiments were performed to evaluate cognitive functions. To examine long-term potentiation (LTP), excitatory postsynaptic potential on Schaffer collateral in response to theta burst stimulation on CA1 was recorded on the acute hippocampal slices. Behavioral and electrophysiological experiments were performed one day after the last injection. Slices after stimulation were applied to Western blotto analyze phosphorylation of AMPA receptor (Ser831, Ser845).

[Results] Mice with METH in the NAc showed cognitive impairment in the novel object recognition test. LTP and phosphorylation of AMPA receptors were reduced in mice treated with METH.

[Conclusion] Local METH administration in the NAc is suggested to suppress hippocampal synaptic transmission to cause cognitive dysfunction.