Dynamic oscillations of local field potential in the nucleus accumbens and dorsal hippocampus during repeated administration, abstinence, and low-dose challenge of methamphetamine exposure in a mouse model�

Abstract

Drug addiction is marked by significant brain adaptations, including changes in neural dynamics within reward-related brain areas that reinforce compulsive drug-seeking behaviors. This study examined depressive-like behavior oscillatory patterns of local field potentials (LFPs) in the nucleus accumbens (NAc) and dorsal hippocampus (dHP) on day 1 of 5 mg/kg methamphetamine (METH) repeated administration (once daily, i.p.), day 8 of METH abstinence and final day with a low-dose of METH challenge (1mg/kg) in METH group of C57BL/6 mice. The parallel control group received treatment with saline. The analyses of NAc LFP showed that METH group significantly decreased theta power in all 3 phases and increased low and high gamma power in repeated administration phases and challenge phases. Additionally, the dHP LFP was found to significantly reduce alpha2 power in both the repeated administration and challenge phases, but increase low gamma power in these phases. Phase-amplitude coupling (PAC) analyses also confirmed significant changes in the NAc but not dHP. Both frequency for amplitude and maximal modulation index of NAc theta-high gamma were significantly decreased in repeated administration and challenge METH phases. After 8-day METH abstinence, tail suspension test (TST) and forced swimming test (FST) were performed. Immobility time analyses revealed no significant difference between groups for both TST and FST. Analyses of NAc LFP during TST confirmed that mean power frequency was significantly increased for slow frequency and decreased for fast frequency. The sleep analysis also showed reduced NREM sleep in repeated administration and challenge, but not abstinence phase of METH group. These findings suggest that short-term exposure to repeated METH administration heightens sensitivity in the reward system, inducing neural sensitization, altering sleep architecture and changing neural signaling during depressive-like behavioral test. This provides insight into how short-term neural stimulation may contribute to the development of addictive behaviors. Minimizing detrimental neural changes, particularly sleep structure, could represent a potential marker for therapeutic applications in managing addiction and fostering recovery.

??????????????????????????????????????????????? ??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????? ???????????????????????????????????????????????????????? local field potential (LFPs) ???????????? nucleus accumbens (NAc) ??? dorsal hippocampus (dHP) 1) ?????? 1 ????????????????????????????? 5 ??. ????????????? 1 ??. (5 mg/kg methamphetamine, METH) ??????????????????????????????????? 2) ?????? 8 ??????????? METH ????????? challenge ?????????? METH ???????????????????????????????? C57BL/6 ??????????????????????????????????????? ?????????????????????????????? NAc ??????????????????? METH ????????????????? theta ?????????? 3 ?????????????????????????? low ??? high gamma ??????????????????????????????????????????????????????? challenge ????????? ????? LFP ?? dHP ????????????????????????????? alpha2 ??????????????????????????????? challenge ??????????????????????? low gamma ?????????????????? ???????????????? phase-amplitude coupling ????????????????????????????????????? NAc ?????????? dHP ?????????? frequency for amplitude ?????? maximal modulation index ??? theta-high gamma coupling ?????????????????????????????????? METH ???????????????????????? challenge ???? METH ???????????????????????? METH ???????? 8 ??????? ?????????? tail suspension test (TST) ??? force swimming test (FST) ????????????????? immobility time ????????????????????????????????????????????????? ??????????????????????????? LFP ???????????? NAc ?????????? TST ???? ???????? mean power frequency ??????????? slow frequency ????????? fast frequency ??????????????? ????????? ?????????????????????????????????????????????????????? non-rapid eye movement ???????????? METH ????????????????????? challenge ????????????????????????????????? METH ??????????????????????????????? ????????? METH ???? ??????????????? ????????????????????????????????????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????? ??????????????????????????????????????????????????????????? ???????????????????????????????????????????????????????????????????????? ????????????????????????????????????????????????? ????????????????????????????????????????? ?????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????