Effect of acute and chronic administration of methamphetamine on calcium-calmodulin dependent protein kinase II activity in the rat brain.
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.
Akiyama
K
K
Department of Neuropsychiatry, Okayama Universiy, Medical School, Japan. kazufuak@cc.okayama-u.ac.jp
Suemaru
J
J
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases