Microglia depletion by PLX3397 has no effect on cocaine-induced behavioral sensitization in male mice

Ching Mei Wu; Ted Weita Lai

doi:10.1016/j.brainres.2021.147391

Microglia depletion by PLX3397 has no effect on cocaine-induced behavioral sensitization in male mice

Brain Res. 2021 Feb 25:1761:147391. doi: 10.1016/j.brainres.2021.147391. Online ahead of print.

Authors

Ching Mei Wu¹, Ted Weita Lai²

Affiliations

¹ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
² Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Drug Development Center, China Medical University, Taichung, Taiwan; Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan. Electronic address: ted.weita@me.com.

PMID: 33639199
DOI: 10.1016/j.brainres.2021.147391

Abstract

Cocaine and other addictive drugs are known to stimulate microglia, and microglia in turn have been shown to play roles in both the development and mitigation of drug dependence. For instance, cocaine can directly bind to surface receptors on microglia and trigger their release of interleukin-1β, which promotes addictive behaviors; however, cocaine also indirectly stimulates microglia by elevating dopamine, which causes microglia to impair long-lasting neuronal changes related to cocaine use. The seemingly opposing roles of microglia beg the question of what the net effect of microglial presence is on cocaine-induced behavioral changes. Here, we depleted microglia from the mouse brain by treating mice with PLX3397 and subjected the mice to cocaine-induced behavioral sensitization, a model for studying long-lasting neuronal changes associated with drugs of abuse. Although cocaine treatment had little effect on microglial abundance, PLX3397 treatment dramatically decreased the number of microglia in the nucleus accumbens and hippocampus in control mice and in mice subjected to cocaine sensitization. Importantly, loss of microglia did not appear to affect either the acute locomotor response to cocaine treatment or sensitization after repeated doses of cocaine. In conclusion, while our data do not contradict previous findings indicating that different microglial-derived factors can have seemingly opposite effects on behaviors associated with cocaine use, they suggest that microglia do not have a net effect on cocaine-induced long-lasting behavioral changes.

Keywords: Addiction; Cocaine; Microglia; PLX3397; Pexidartinib; Sensitization.