Exercise modulates central and peripheral inflammatory responses and ameliorates methamphetamine-induced anxiety-like symptoms in mice

Abstract

Anxiety-like symptoms are common symptoms of methamphetamine (METH) users, especially in the acute withdrawal period, which is an important factor for the high relapse rate during METH acute withdrawal. Exercise has been demonstrated to relieve anxiety-like symptoms during METH withdrawal, but the underlying mechanisms of this anti-anxiety effect are still unclear. Activated microglia and abnormal neuroinflammation play an important role in the pathogenesis of anxiety-like symptoms after METH withdrawal. Moreover, peripheral immune factors were also significantly associated with anxiety symptoms. However, the effects of treadmill exercise on microglial function and neuroinflammation in the striatum and hippocampus during acute METH withdrawal have not been reported. In the current study, we found severe peripheral immune dysfunction in METH users during acute withdrawal, which may in part contribute to anxiety symptoms during METH acute withdrawal. We also showed that 2 weeks of METH exposure induced anxiety-like symptoms in the acute withdrawal period. Additionally, METH exposure resulted in increased microglial activation and proinflammatory cytokines released in the mouse striatum and hippocampus during acute withdrawal. We next evaluated the effects of treadmill exercise in countering anxiety-like symptoms induced by METH acute withdrawal. The results showed that anxiety-like symptoms induced by acute METH withdrawal were attenuated by coadministration of treadmill exercise. In addition, treadmill exercise counteracted METH-induced microglial activation in the mouse striatum and various subregions of the hippocampus. Furthermore, treadmill exercise also reversed the increase in proinflammatory cytokines induced by acute METH withdrawal in the mouse striatum, hippocampus and serum. Our findings suggest that the anti-anxiety effect of treadmill exercise may be mediated by reducing microglial activation and regulating central and peripheral inflammatory responses.

GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal

“…METH use may damage brain structure and function, leading to negative emotions including anxiety and depression [ [20] , [21] , [22] ]. Even several years after treatment, those in recovery from METH addiction may continue to experience varying degrees of depression [ 23 ].…”

“…Different dose regimens including a single high-dose (30 mg/kg) [ 27 ], 5 mg/kg for five days [ 28 ], and 8 weeks of METH administration [ 29 ], have been employed; all of these result in the manifestation of anxiety- or depression-like behavior. Such effects were also observed following intraperitoneal injections of 5 mg/kg METH for 21 consecutive days, as well as with escalating doses for 14 consecutive days [ 20 , 21 ]. The dosage of 10 mg/kg for 14 days applied in our study was informed by these previous studies and we successfully identified these psychological conditions.…”

Effect of Aerobic Exercise on Intestinal Microbiota with Amino Acids and Short-Chain Fatty Acids in Methamphetamine-Induced Mice

“…After the CPP was finished, the exercise intervention was started for the mice in group Ea, and the aerobic exercise method used was running platform exercise (SA101, Saionce, nanjing, Jiangsu, China) as previously described [ 47 ] with some adjustments. The slope of the running platform was set to 0° and increased at 8 m/min to 12 m/min (3 days) and finally at 12 m/min for 60 min for 11 days for 2 weeks [ 47 , 48 ]. The time for running table practice was from 19:00 to 20:00.…”

Effects of exercise of different intensities on withdrawal symptoms among people with substance use disorder: a systematic review and meta-analysis

“…There is extensive work in the literature ( Centanni et al, 2022 ; Li et al, 2022 ; Re et al, 2022 ) demonstrating that exercise can improve withdrawal symptoms and reduce relapse rates. Therefore, exercise has been considered an excellent adjunct treatment to existing treatment regimens ( Wang et al, 2014 ; He et al, 2021 ; Salem et al, 2022 ).…”