¹Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA

Correspondence: Dr BP Sokolov, Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Tel: +1 410 550 1582x391; Fax: +1 410 550 2742; E-mail: Bsokolov@intra.nida.nih.gov

Received 21 February 2005; Revised 7 June 2005; Accepted 5 August 2005; Published online 28 September 2005.

Abstract

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, GSK3, 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 GSK3 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.