Cue-induced drug craving and seeking progressively increases during abstinence. This "incubation of drug craving" phenomenon has been observed in both laboratory animals and humans. Preclinical studies identified several neural mechanisms underlying incubation of drug craving after forced abstinence, primarily focusing on cocaine. Recently, studies started focusing on another powerful psychostimulant, methamphetamine (Meth), and developed new incubation procedures (choice-induced and punishment-induced abstinence). Here, we review mechanistic studies at the circuit, synaptic and molecular levels on incubation of Meth craving. First, we provide an overview of neural adaptations associated with prolonged forced abstinence after extended-access Meth self-administration. Next, we review studies examining the causal roles of discrete brain regions and associated circuits, glutamate transmission, histone deacetylase 5 and oxytocin in incubation of Meth craving after forced abstinence. Lastly, we review causal and correlational studies examining the mechanisms underlying incubation of Meth craving after choice-induced voluntary abstinence and punishment-induced abstinence, respectively. We conclude by discussing the translational potential of these mechanistic studies in Meth relapse prevention in human drug users.
Keywords: Addiction; Circuit; Incubation of craving; Methamphetamine; Molecular; Relapse.
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