Theta and gamma modulation in the nucleus accumbens as drivers of neurophysiological responses to acute methamphetamine sensitization in mice.

Abstract

Methamphetamine (METH) has well-documented long-term effects on the brain, including increased psychomotor activity and behavioral sensitization. However, its immediate effects on the brain's reward system following acute exposure, which may contribute to the development of addiction, are less understood. This study aimed to investigate the effects of acute METH on brain oscillations in the nucleus accumbens of C57BL/6 mice. Mice in the METH group received 5 mg/kg of METH for 5 days during the conditioning phase, followed by an 8-day abstinence period. Afterward, they underwent a 6-minute tail suspension test and were given a 1 mg/kg METH challenge. Local field potential (LFP) data were analyzed for percent total power, mean frequency indices, and phase-amplitude coupling (PAC) to assess the neural effects of METH exposure across these phases. A reduction in theta power was observed across the conditioning, abstinence, and challenge phases of METH exposure. The subsequent METH challenge enhanced gamma oscillations, and PAC analysis revealed a consistent theta-gamma coupling index during both the METH administration and challenge phases. It highlights the sensitivity of the reward system to intense, short-term drug exposure, providing new insights into how acute neural stimulation may contribute to the development of addictive behaviors, reinforcing the brain's vulnerability to drug-induced changes in neural circuitry.