Roles of dopaminergic innervation of nucleus accumbens shell and dorsolateral caudate-putamen in cue-induced morphine seeking after prolonged abstinence and the underlying D1- and D2-like receptor mechanisms in rats

Jun Gao, Yonghui Li, Ning Zhu, Stephen Brimijoin, Nan Sui

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Drug-associated cues can elicit relapse to drug seeking after abstinence. Studies with extinction-reinstatement models implicate dopamine (DA) in the nucleus accumbens shell (NAshell) and dorsolateral caudate-putamen (dlCPu) in cocaine seeking. However, less is known about their roles in cue-induced opiate seeking after prolonged abstinence. Using a morphine self-administration and abstinence-relapse model, we explored the roles of NAshell and dlCPu DA and the D1/D2-like receptor mechanisms underlying morphine rewarding and/or seeking. Acquisition of morphine self-administration was examined following 6-Hydroxydopamine hydrobromide (6-OHDA) lesions of the NAshell and dlCPu. For morphine seeking, rats underwent 3 weeks' morphine self-administration followed by 3 weeks' abstinence from morphine and the training environment. Prior to testing, 6-OHDA, D1 antagonist SCH23390, or D2 antagonist eticlopride was locally injected; then rats were exposed to morphine-associated contextual and discrete cues. Results show that acquisition of morphine self-administration was inhibited by NAshell (not dlCPu) lesions, while morphine seeking was attenuated by lesions of either region, by D1 (not D2) receptor blockade in NAshell, or by blockade of either D1 or D2 receptors in dlCPu. These data indicate a critical role of dopaminergic transmission in the NAshell (via D1-like receptors) and dlCPu (via D1- and D2-like receptors) in morphine seeking after prolonged abstinence.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalJournal of Psychopharmacology
Volume27
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Abstinence
  • D1-like
  • D2-like
  • dorsolateral caudate-putamen (dlCPu)
  • morphine
  • nucleus accumbens shell (NAshell)
  • seeking
  • self-administration

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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