Alterations in calmodulin mRNA expression and calmodulin content in rat brain after repeated, intermittent amphetamine.
To assess whether calmodulin (CaM) gene expression could have a role in behavioral sensitization induced by repeated, intermittent amphetamine, CaM protein and mRNA of the three separate CaM genes were measured in several different brain areas from rats repeatedly administered saline or amphetamine. Rats were injected twice weekly for five weeks, followed by one week of withdrawal. CaM protein and mRNA were measured in dorsal striatum, limbic forebrain, prefrontal cortex, ventral mesencephalon and piriform cortex. There were increases of CaM protein content and decreases of CaM I mRNA in the dorsal striatum and prefrontal cortex. CaM II mRNA was also decreased in the dorsal striatum. A decrease of CaM protein and an increase of CaM I mRNA were found in the ventral mesencephalon. There was no change of CaM protein in the limbic forebrain, although a decrease of CaM I mRNA was detected. CaM protein and mRNA were not altered in the piriform cortex. Our findings demonstrate that both CaM content and mRNA are altered after an amphetamine regimen leading to sensitization. The fact that the changes in CaM content and mRNA are in dopaminergic brain areas associated with sensitization suggests that CaM could contribute to neurochemical events underlying behavioral sensitization to amphetamine.
Michelhaugh
S K
SK
Department of Pharmacology, 2220E MSRBIII, University of Michigan Medical School, Ann Arbor, MI 48109-0634, USA.
Pimputkar
G
G
Gnegy
M E
ME
D017398:Alternative Splicing; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry; D002147:Calmodulin / Q000032:analysis* / Q000235:genetics*; D003342:Corpus Striatum / Q000737:chemistry; D004334:Drug Administration Schedule; D005260:Female; D007274:Injections, Intraperitoneal; D008636:Mesencephalon / Q000737:chemistry; D017397:Prefrontal Cortex / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002147:Calmodulin; D012333:RNA, Messenger; D000661:Amphetamine