Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice
摘要Drug addiction is characterized by relapse when addicts are re-exposed to drug-associated environmental cues,but the neural mechanisms underlying cue-induced relapse are unclear.In the present study we investigated the role of a specific dopaminergic(DA)pathway from ventral tegmental area(VTA)to nucleus accumbens core(NAcore)in mouse cue-induced relapse.Optical intracranial self-stimulation(oICSS)was established in DAT-Cre transgenic mice.We showed that optogenetic excitation of DA neurons in the VTA or their projection terminals in NAcore,NAshell or infralimbic prefrontal cortex(PFC-IL)was rewarding.Furthermore,activation of the VTA-NAcore pathway alone was sufficient and necessary to induce reinstatement of oICSS.In cocaine self-administration model,cocaine-associated cues activated VTA DA neurons as assessed by intracellular GCaMP signals.Cue-induced reinstatement of cocaine-seeking was triggered by optogenetic stimulation of the VTA-NAcore pathway,and inhibited by chemogenetic inhibition of this pathway.Together,these results demonstrate that cue-induced reinstatement of reward seeking is in part mediated by activation of the VTA-NAcore DA pathway.
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