Involvement of signal transduction cascade via dopamine-D1 receptors in phencyclidine dependence

Yukihiro Noda, Toshitaka Nabeshima

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


We investigated the molecular mechanisms of development to phencyclidine (PCP)-indnced rewarding effect by using tyrosine hydroxylase (TH) heterozygous (TH+/-) mice. PCP (8 mg/kg) induced the place preference in wild-type mice pretreated with PCP (10 mg/kg/day for 28 days). The place preference induced by PCP is attenuated by 6-hydroxydopamine, a dopaminergic neurotoxin, and (+) SCH-23390, a dopamine-D1 receptor antagonist, but not by DSP-4, a noradrenergic neurotoxin, and (-) sulpiride, a dopamine-D2 receptor antagonist. In TH+/- mice pretreated with PCP (10 mg/kg/day for 28 days), no PCP (8 mg/kg)-induced place preference was observed. In wild-type mice pretreated with PCP, the levels of cAMP, cAMP response element binding protein (CREB), and c-fos mRNA in the nucleus accumbens were increased. The levels of cAMP, CREB, and c-fos mRNA in tine nucleus accumbens were not increased by the same treatment schedule of PCP in TH+/- mice. These findings suggest that changes in dopaminergic and/or cAMP signal cascades induced by repeated PCP treatment play an important role in the development of PCP-induced rewarding effect.

Original languageEnglish
Pages (from-to)62-68
Number of pages7
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • History and Philosophy of Science


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