Drug addiction is hypothesized as a transition from NAc-DA dependent goal-directed drug-taking to dlCPu-DA dependent habitual drug-seeking. Evidence from cocaine addiction studies suggests DA in NAc and dlCPu regulates addiction formation and cocaine seeking respectively, however, less is known about their roles in opiate-addiction formation and opiate seeking. Accordingly, current study explored roles of NAc and dlCPu in morphine-addiction formation and cue-induced morphine seeking and the underlying dopaminergic mechanisms. 1) We constructed the morphine self-administration model, and explored morphine dose effect, and effects of training time, food reinforcement training on self-administration behaviors. Results showed: we successfully constructed the morphine self-administration model using a FR1 reinforcing procedure; morphine infusions reduced while morphine intake doses increased as long as the injection dosage increased from 0.1 to 1.0 mg/kg; daily long access training did not but food reinforcement training did reduce the number of sessions to get the stable self-administration behavior; the incubation effect of morphine craving was shown in the constructed abstinence-relapse model. 2) To explore the roles of dopaminergic innervation in NAc shell and dlCPu in morphine-addiction formation or morphine seeking, rats were microinjected with 6-OHDA, and results showed that the acquisition of morphine self-administration was inhibited by lesions in NAc shell (not dlCPu), while morphine seeking was attenuated by lesions of either region. 3) To explore the D1- and D2-like receptor mechanisms in NAc shell and dlCPu, D1 antagonist SCH23390, or D2 antagonist eticlopride was locally injected prior to the seeking test, and results showed that morphine seeking was attenuated by D1 (not D2)-like receptor blockade in NAshell, or by blockade of either D1- or D2-like receptors in dlCPu. 4) To explore effects of morphine seeking on dopaminergic activity in NAc core, shell and dlCPu, microdialysis samples were got prior to or during morphine seeking test after abstinence for 1 day or 21 days, and results showed that morphine seeking evoked a significant elevation of DOPAC in dlCPu (not NAc core or shell) after abstinence for 21 days, while DOPAC or HVA in all three regions was not changed during morphine seeking after abstinence for 1 day. These data indicate a critical role of dopaminergic innervation in NAc in acquisition of morphine self-administration, and a critical role of dopaminergic transmission in the NAc (via D1-like receptors) and dlCPu (via D1- and D2-like receptors) in cue-induced morphine seeking after prolonged abstinence. These findings were important for elucidating different mechanisms of rewarding system and habitual system in formation and relapse. Key Words：nucleus accumbens (NAc); dorsolateral caudate-putman (dlCPu); dopamine; morphine; addiction; seeking
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