摘要Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior,which has been linked with aberrant synaptic plasticity.An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3)inflammasome.3'-Deoxyadenosin,an active component of the Chinese fungus Cordyceps militaris,has strong anti-inflammatory effects.However,whether 3'-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear.We first observed that 3'-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons.Furthermore,we found that 3'-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity.We also found that 3'-deoxyadenosin decreased the expression of NLRP3 and neuronal injury.Importantly,a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior,attenuated the impaired synaptic plasticity,and prevented neuronal damage.Finally,NLRP3 activation reversed the effect of 3'-deoxyadenosin on behavior and synaptic plasticity,suggesting that the anti-neuroinflammatory mechanism of 3'-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior.Taken together,3'-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.