TY - JOUR
T1 - Aberrant Behavioral Sensitization by Methamphetamine in Junctophilin-Deficient Mice
AU - Moriguchi, Shigeki
AU - Nishi, Miyuki
AU - Sasaki, Yuzuru
AU - Takeshima, Hiroshi
AU - Fukunaga, Koji
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology, and the Ministry of Health and Welfare of Japan (24659024 and 24102505 to K.F.; 20790398 to S.M.), the Smoking Research Foundation (to K.F.), the Takeda Science Foundation (to S.M.), and the Suzuken Memorial Foundation (to S.M.). Authors have no conflict of interest in this work.
Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2015/4
Y1 - 2015/4
N2 - Junctophilins (JPs) expressed in the endoplasmic/sarcoplasmic reticulum (ER/SR) interact with the plasma membrane, thereby constructing junctional membrane complexes (JMC). We here reported that double-knockout mice lacking both JP3 and JP4 (JP-DKO mice) exhibit aberrant synaptic plasticity in the corticostriatal circuits and irregular methamphetamine (METH)-induced behavioral sensitization when METH (1.0 mg/kg) was administrated six consecutive days and assessed the striatal glutamatergic population spike (PS) by stimulation of cortical white matter. When we assessed the striatal PS by stimulation of cortical white matter, the long-term depression (LTD) was observed in JP-DKO mouse striatum similar to that in control (JP-double hetero mice (JP-DHE mice)). Importantly, LTD converted to long-term potentiation (LTP) following chronic METH treatment concomitant with behavioral sensitization in JP-DHE mice. LTD in JP-DKO mice, however failed to convert to LTP with lacks of behavioral sensitization. LTP impairment in JP-DKO mice was restored by pretreatment with FK506, calcineurin (CaN) inhibitor, but not with apamin, SK channel inhibitor. In immunoblotting analyses, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation was significantly increased following METH treatment in the striatum of JP-DHE mice. However, CaMKII autophosphorylation did not changed by METH treatment in the striatum of JP-DKO mouse. The increased CaMKII autophosphorylation was closely associated with elevated CaN activity in JP-DKO mice. The lack of increased CaMKII activity in JP-DKO mice was correlated with the impaired METH-induced behavioral sensitization. Thus, elevated CaN and aberrant CaMKII activities in the striatum of JP-DKO mice likely accounts for lack of METH-induced behavioral sensitization.
AB - Junctophilins (JPs) expressed in the endoplasmic/sarcoplasmic reticulum (ER/SR) interact with the plasma membrane, thereby constructing junctional membrane complexes (JMC). We here reported that double-knockout mice lacking both JP3 and JP4 (JP-DKO mice) exhibit aberrant synaptic plasticity in the corticostriatal circuits and irregular methamphetamine (METH)-induced behavioral sensitization when METH (1.0 mg/kg) was administrated six consecutive days and assessed the striatal glutamatergic population spike (PS) by stimulation of cortical white matter. When we assessed the striatal PS by stimulation of cortical white matter, the long-term depression (LTD) was observed in JP-DKO mouse striatum similar to that in control (JP-double hetero mice (JP-DHE mice)). Importantly, LTD converted to long-term potentiation (LTP) following chronic METH treatment concomitant with behavioral sensitization in JP-DHE mice. LTD in JP-DKO mice, however failed to convert to LTP with lacks of behavioral sensitization. LTP impairment in JP-DKO mice was restored by pretreatment with FK506, calcineurin (CaN) inhibitor, but not with apamin, SK channel inhibitor. In immunoblotting analyses, calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation was significantly increased following METH treatment in the striatum of JP-DHE mice. However, CaMKII autophosphorylation did not changed by METH treatment in the striatum of JP-DKO mouse. The increased CaMKII autophosphorylation was closely associated with elevated CaN activity in JP-DKO mice. The lack of increased CaMKII activity in JP-DKO mice was correlated with the impaired METH-induced behavioral sensitization. Thus, elevated CaN and aberrant CaMKII activities in the striatum of JP-DKO mice likely accounts for lack of METH-induced behavioral sensitization.
KW - Behavioral sensitization
KW - Calcineurin
KW - Calcium/calmodulin-dependent protein kinase II
KW - Junctophilin
KW - Long-term potentiation
KW - Striatum
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U2 - 10.1007/s12035-014-8737-2
DO - 10.1007/s12035-014-8737-2
M3 - Article
C2 - 24848513
AN - SCOPUS:84939886386
VL - 51
SP - 533
EP - 542
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
IS - 2
ER -