Role of convergent activation of glutamatergic and dopaminergic systems in the nucleus accumbens in the development of methamphetamine psychosis and dependence

Masayuki Miyazaki, Yukihiro Noda, Akihiro Mouri, Kazuto Kobayashi, Masayoshi Mishina, Toshitaka Nabeshima, Kiyofumi Yamada

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Methamphetamine (Meth) abuse can result in long-lasting psychosis and dependence. The nucleus accumbens (NAc), which controls psychomotor and reward behaviours, is an important interface between the limbic system and receives convergent projections from dopaminergic and glutamatergic terminals. This study investigated the involvements of dopaminergic and glutamatergic transmission in the development of Meth psychosis and dependence by using tyrosine hydroxylase heterozygous mutant (TH+/-) mice and N-methyl-d-aspartate receptor knockout (NR2A-/-) mice. Repeated treatment with Meth (1Â mg/kg s.c.) for 7Â d in wild-type mice led to the development of behavioural abnormalities such as hyperactivity, sensory motor gating deficits and place preference. Associated with the behavioural changes, repeated treatment with Meth led to protein kinase A activation and phosphorylation of Ca 2+/calmodulin kinase II and cyclic AMP response element binding protein in the NAc. In contrast, TH+/- and NR2A-/- mice displayed neither behavioural abnormalities nor activation of intracellular signalling pathways in the NAc. These results suggest that both dopaminergic and glutamatergic transmission play a crucial role in the development of Meth psychosis and dependence, which are associated with convergent activation of intracellular signalling pathways in the NAc.

Original languageEnglish
Pages (from-to)1341-1350
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number6
DOIs
Publication statusPublished - 01-07-2013
Externally publishedYes

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Methamphetamine
Nucleus Accumbens
Psychotic Disorders
Sensory Gating
Hyperkinesis
Cyclic AMP Response Element-Binding Protein
Limbic System
Calcium-Calmodulin-Dependent Protein Kinases
Tyrosine 3-Monooxygenase
Cyclic AMP-Dependent Protein Kinases
Reward
Knockout Mice
Phosphorylation

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "Role of convergent activation of glutamatergic and dopaminergic systems in the nucleus accumbens in the development of methamphetamine psychosis and dependence",
abstract = "Methamphetamine (Meth) abuse can result in long-lasting psychosis and dependence. The nucleus accumbens (NAc), which controls psychomotor and reward behaviours, is an important interface between the limbic system and receives convergent projections from dopaminergic and glutamatergic terminals. This study investigated the involvements of dopaminergic and glutamatergic transmission in the development of Meth psychosis and dependence by using tyrosine hydroxylase heterozygous mutant (TH+/-) mice and N-methyl-d-aspartate receptor knockout (NR2A-/-) mice. Repeated treatment with Meth (1{\^A} mg/kg s.c.) for 7{\^A} d in wild-type mice led to the development of behavioural abnormalities such as hyperactivity, sensory motor gating deficits and place preference. Associated with the behavioural changes, repeated treatment with Meth led to protein kinase A activation and phosphorylation of Ca 2+/calmodulin kinase II and cyclic AMP response element binding protein in the NAc. In contrast, TH+/- and NR2A-/- mice displayed neither behavioural abnormalities nor activation of intracellular signalling pathways in the NAc. These results suggest that both dopaminergic and glutamatergic transmission play a crucial role in the development of Meth psychosis and dependence, which are associated with convergent activation of intracellular signalling pathways in the NAc.",
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Role of convergent activation of glutamatergic and dopaminergic systems in the nucleus accumbens in the development of methamphetamine psychosis and dependence. / Miyazaki, Masayuki; Noda, Yukihiro; Mouri, Akihiro; Kobayashi, Kazuto; Mishina, Masayoshi; Nabeshima, Toshitaka; Yamada, Kiyofumi.

In: International Journal of Neuropsychopharmacology, Vol. 16, No. 6, 01.07.2013, p. 1341-1350.

Research output: Contribution to journalArticle

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AU - Yamada, Kiyofumi

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