Lithium inhibits the reverse tolerance and the c-Fos expression induced by methamphetamine in mice.

To elucidate the mechanism of psychostimulant-induced reverse tolerance, the effects of lithium on ambulatory activity and cerebral c-Fos protein expression were investigated in mice injected with methamphetamine (2 mg/kg, s.c., 1-5 times). The ambulatory activity enhanced by either acute or chronic methamphetamine injection was delayed or diminished by LiCl pretreatment (170 mg/kg, s.c., 1 h before methamphetamine). The c-Fos expression in the dorsal lateral geniculate nucleus and in the striatum was significantly increased by acute but not chronic injection of methamphetamine, and the increases were significantly suppressed by LiCl pretreatment. Although how the Li-sensitive c-Fos expressions in the dorsolateral geniculate nucleus and striatum are related to methamphetamine-induced behavioral excitation is unclear, these results suggest that lithium at least functionally interferes with the formation of the state of reverse tolerance to methamphetamine in the mouse.