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Glutamatergic neurotransmission and protein kinase C play a role in neuron–glia communication during the development of methamphetamine‐induced psychological dependence
Author(s) -
Miyatake Mayumi,
Narita Minoru,
Shibasaki Masahiro,
Nakamura Atsushi,
Suzuki Tsutomu
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04325.x
Subject(s) - meth , dnqx , glutamate receptor , methamphetamine , glutamatergic , astrocyte , protein kinase c , neuron , neuroscience , chelerythrine , ifenprodil , neurotransmission , ampa receptor , microbiology and biotechnology , protein kinase a , biology , chemistry , pharmacology , central nervous system , receptor , signal transduction , kinase , biochemistry , monomer , organic chemistry , acrylate , polymer
Methamphetamine (METH) is a strongly addictive psychostimulant that dramatically affects the central nervous system (CNS). On the other hand, protein kinase C (PKC) plays a major role in cellular regulatory and signalling processes that involve protein phosphorylation. The purpose of this study was to investigate the role of neuronal and astrocytic PKC in changes in the central glutamatergic system induced by METH. We show here that in vitro treatment with METH caused the phosphorylation of both neuronal and astrocytic PKC and the activation of astrocytes in cortical neuron/glia co‐cultures. Treatment of cortical neuron/glia co‐cultures with either the PKC activator phorbol 12,13‐dibutyrate (PDBu) or glutamate also caused the PKC‐dependent activation of astrocytes. The PKC inhibitor chelerythrine suppressed the Ca 2+ responses to glutamate in both cortical neurons and astrocytes. Moreover, a low concentration of PDBu significantly enhanced the Ca 2+ responses to glutamate, but not to dopamine, in both cortical neurons and astrocytes. Notably, treatment with METH also enhanced the Ca 2+ responses to glutamate in cortical neurons. The activation of astrocytes induced by METH was also reversed by co‐treatment with glutamate receptor antagonists (ifenprodil, DNQX or MPEP) in cortical neuron/glia co‐cultures. In the conditioned place preference paradigm, intracerebroventricular administration of glutamate receptor antagonists (ifenprodil, DNQX or MPEP) attenuated the METH‐induced rewarding effect. These findings provide evidence that the changes in PKC‐dependent neuronal and astrocytic glutamatergic transmission induced by METH may, at least in part, contribute to the development of psychological dependence on METH.