Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness.
Aggressive behaviors have been reported in patients who suffer from some psychiatric disorders, and are common in methamphetamine (METH) abusers. Herein, we report that multiple (but not single) injections of METH significantly increased aggressiveness in male CD-1 mice. This increase in aggressiveness was not secondary to METH-induced hyperactivity. Analysis of protein expression using antibody microarrays and Western blotting revealed differential changes in MAP kinase-related pathways after multiple and single METH injections. There were statistically significant (p<0.05) decreases in MEK1, Erk2p, GSK3alpha, 14-3-3e, and MEK7 in the striata of mice after multiple injections of METH. MEK1 was significantly decreased also after a single injection of METH, but to a much lesser degree than after multiple injections of METH. In the frontal cortex, there was a statistically significant decrease in GSK3alpha after multiple (but not single) injections of METH. These findings suggest that alterations in MAP kinase-related pathways in the prefronto-striatal circuitries might be involved in the manifestation of aggressive behaviors in mice.
Sokolov
Boris P
BP
Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD 21224, USA. Bsokolov@intra.nida.nih.gov
Cadet
Jean L
JL
D000374:Aggression / Q000187:drug effects* / Q000502:physiology; D019969:Amphetamine-Related Disorders / Q000201:enzymology* / Q000503:physiopathology / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects
D008694:Methamphetamine; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D048369:MAP Kinase Kinase 1