Electroacupuncture prevents cocaine-induced conditioned place preference reinstatement and attenuates \u0394FosB and GluR2 expression

Ai T M Nguyen,Jaung-Geng Lin,Cheng-Hao Tu,Peddanna Kotha,Szu-Yu Chien,Hsien-Yuan Lane,Tran V B Quach,Yi-Hung Chen,Iona J Macdonald

doi:10.1038/s41598-021-93014-0

Abstract

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. The transcription factor delta-FosB (ΔFosB) plays a critical role in behavior and pathology after chronic use of cocaine. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models. This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). EA at LI4 and LI11 significantly prevented cue-induced cocaine CPP reinstatement, whereas needle insertion without electrical stimulation at these acupoints had no such effect. EA also significantly attenuated cocaine-induced increases in ΔFosB and GluR2 expression in the NAc. Unexpectedly, these effects were reversed when GBP was combined with EA. Treatment with EA at LI4 and LI11 prevented cocaine-induced increases in dendritic spine density in the NAc core and shell. Our results suggest that EA at LI4 and LI11 may prevent cocaine relapse by modulating ΔFosB and GluR2 expression, as well as dendritic spine density.

Highlights

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse
Two-way analysis of variance (ANOVA) revealed significant interaction effects (F[9,72] = 4.031, p < 0.001) between groups (no intervention [CO], EA treatment [CO + EA], manual acupuncture (MA) treatment [CO + Manual acupuncture (MA)], and 2% lidocaine injection followed by EA treatment [CO + LIDO + EA]) and phases
Post-hoc analysis revealed that conditioned place preference (CPP) scores were significantly increased in the POST phase compared with the PRE phase in all groups (CO group: p < 0.05; CO + EA group: p < 0.01; CO + MA group: p < 0.01; CO + LIDO + EA group: p < 0.01), whereas CPP scores were significantly decreased in the Extinction of cocaine CPP (EXT) phase compared with the POST phase (CO group: p < 0.05; CO + EA group: p < 0.001; CO + MA group: p < 0.01; CO + LIDO + EA group: p < 0.05)

Summary

Introduction

Acupuncture has been used for treating drug addiction since the 1970s, but little is known about the mechanisms by which acupuncture affects drug cue-induced relapse. ΔFosB regulates glutamate receptor signaling and dendritic spine morphology in animal models This experimental study compared the effects of electroacupuncture (EA) at acupoints LI4 and LI11 with those of another potentially beneficial intervention, gabapentin (GBP), alone or in combination, on reinstatement of cocaine-induced conditioned place preference (CPP) and levels of ΔFosB and glutamate receptor subunit 2 (GluR2) expression in the nucleus accumbens (NAc). The overexpression of ΔFosB protein induced by chronic cocaine administration leads to changes in the glutamatergic synapses in the NAc, including increased dendritic spine density[9]. The experimental evidence shows that acupuncture modulates molecular abnormalities induced by exposure to addictive substances, but evidence is lacking as to the effects of acupuncture on glutamatergic neurotransmission and how acupuncture reduces the reinstatement of drug-seeking behavior. We sought to determine whether treatment with combined GBP and EA would have any beneficial effect upon cue-induced cocaine seeking and relapse

Methods

Results

Conclusion