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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.
MedLine Citation:
PMID:  23195702     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 mg/kg s.c.) for 7 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 Ca2+/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.
Authors:
Masayuki Miyazaki; Yukihiro Noda; Akihiro Mouri; Kazuto Kobayashi; Masayoshi Mishina; Toshitaka Nabeshima; Kiyofumi Yamada
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-30
Journal Detail:
Title:  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)     Volume:  -     ISSN:  1469-5111     ISO Abbreviation:  Int. J. Neuropsychopharmacol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815893     Medline TA:  Int J Neuropsychopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-10     Citation Subset:  -    
Affiliation:
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University, Graduate School of Medicine, Nagoya, Japan.
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