Effect of Acute and Chronic Administration of Methamphetamine on Calcium-Calmodulin Dependent Protein Kinase II Activity in the Rat Brain

Autor: Junko Suemaru, Kazufumi Akiyama
Rok vydání: 2000
Předmět:
Zdroj: Annals of the New York Academy of Sciences. 914:263-274
ISSN: 0077-8923
Popis: Several lines of evidence have implicated Ca2+/calmodulin (CaM)-dependent protein kinase II (CaM-kinase II), a multifunctional protein kinase, in the regulation of signal transduction after chronic administration of psychostimulants. CaM-Kinase II activities were decreased in discrete brain regions after a single methamphetamine (METH) injection to rats. Pretreatment with either SCH 23390 (a dopamine D1 receptor antagonist) or NMK-801 (an N-methyl-D-aspartate receptor antagonist) prevented the acute METH-induced decrease in CaM-kinase II activity in the parietal cortex, nucleus accumbens, and substantia nigra/ventral tegmental area (SN/VTA). Striatal CaM-kinase II activity was significantly lower than that of the chronic saline-treated controls after a one-week, but not a four-week, abstinence from chronic administration of METH. A METH challenge after a four-week abstinence period decreased CaM-kinase II activity in rats chronically injected with METH to a greater extent than in rats chronically injected with saline. Western blot analysis revealed that protein amount of CaM-kinase II was not altered after a single METH injection or after chronic METH injections, as compared with saline-treated controls. However, amounts of phosphorylated (Thr286) CaM-kinase II in the parietal cortex, striatum, and SN/VTA were significantly decreased at 3 h after an acute METH injection compared with saline-treated controls. It is suggested that dephosphorylation of CaM-kinase II may contribute to the decreased enzyme activities induced by acute METH administration, and that chronic treatment with METH leads to an enhanced capacity of METH to decrease CaM-kinase II activity after an extended withdrawal period.
Databáze: OpenAIRE