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

Yukihiro Noda, Toshitaka Nabeshima

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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
Volume1025
DOIs
Publication statusPublished - 01-01-2004
Externally publishedYes

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Phencyclidine
Dopamine D1 Receptors
Signal transduction
Tyrosine 3-Monooxygenase
Signal Transduction
Cyclic AMP Response Element-Binding Protein
Neurotoxins
Nucleus Accumbens
Sulpiride
Messenger RNA
Oxidopamine
Dopamine Antagonists
Appointments and Schedules
Dopamine
Mouse
Transduction

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

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abstract = "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.",
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Involvement of signal transduction cascade via dopamine-D1 receptors in phencyclidine dependence. / Noda, Yukihiro; Nabeshima, Toshitaka.

In: Annals of the New York Academy of Sciences, Vol. 1025, 01.01.2004, p. 62-68.

Research output: Contribution to journalArticle

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