Amphetamine sensitization elevates CaMKIIbeta mRNA.
Recent studies have shown that the elevation in calcium/calmodulin-dependent protein kinase II (CaMKII) may play an important role in amphetamine-induced dopamine release, as well as in the increase of dopamine D2 receptor high-affinitystates in psychosis. Because amphetamine sensitization is a widely used animal model of psychosis or schizophrenia, we investigated whether amphetamine sensitization results in an overall increase in the alpha and beta subunits of CaMKII. To answer this question, we measured CaMKII alpha and beta subunit mRNA expression using Real-Time Quantitative PCR in amphetamine-sensitized rat striata, compared to saline-treated controls. The results were then standardized to beta-glucuronidase, a housekeeping gene. Our results showed a statistically significant increase in the CaMKII beta subunit, and an increase in the alpha subunit which did not reach statistical significance. Because the levels of both CaMKIIbeta and CaMKIIalpha play a role in neuronal function and synapse formation, the present finding of an elevated level of CaMKII beta and alpha subunit mRNA in the amphetamine-sensitized model of psychosis points to the possibility of dysregulated levels of CaMKII subunits in human psychosis.
Greenstein
Rachel
R
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Novak
Gabriela
G
Seeman
Philip
P
D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D008297:Male; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects*
D000697:Central Nervous System Stimulants; D021122:Protein Subunits; D012333:RNA, Messenger; D000661:Amphetamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005966:Glucuronidase