Addiction biology
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Cue-induced drug seeking progressively increases over time of withdrawal from drug self-administration in rats, a phenomenon called 'incubation of craving'. The underlying mechanisms have been linked to increased expression of brain-derived neurotrophic factor and GluR2-lacking AMPA receptors in the mesolimbic dopamine (DA) system and also to increased extracellular signal-regulated kinase activation in the central amygdala (CeA). ⋯ Here, we report that systemic or local administration of SB-277011A, a highly selective D3 R antagonist, into the NAc (core and shell) or the CeA, but not the dorsal striatum or basolateral amygdala, significantly inhibits expression of incubation of cocaine craving in rats after 2-30 days of withdrawal from previous cocaine self-administration but had no effect on sucrose-seeking behavior in rats after 10-30 days of withdrawal. These data suggest that DA D3 Rs in both the NAc and the CeA play an important role in incubation of cocaine craving in rats and support the potential utility of D3 R antagonists in the treatment of cocaine addiction.