Circuit-specific neural perturbations and recovery in methamphetamine addiction in a mouse model.

Abstract

Drug addiction is characterized by profound brain adaptations, including altered neural circuit dynamics in reward-related regions, which reinforce compulsive drug-seeking behavior. This study investigated the effects of 5 mg/kg methamphetamine (METH) administration on brain activity measured by local field potentials (LFPs) in the nucleus accumbens (NAc) and dorsal hippocampus (dHP) of C57BL/6 mice. The study further examined the sensitivity of these brain regions during an abstinent period on day 8 and following a low-dose METH challenge. METH administration reduced theta power activity and enhanced gamma activity in the NAc, but decreased alpha2 power with specific high gamma increases in the dHP during conditioning and challenge phases. The sleep analysis revealed a reduction in NREM during the conditioning and challenge phases, however, these parameters returned to normal after 8 days abstinence from METH. These findings suggest that repeated METH administration induces neural sensitization and alters sleep architecture. However, the minimization of adverse neural changes, particularly in sleep regulation, highlights potential avenues for therapeutic applications in managing addiction and promoting recovery.