Methamphetamine Causes Alterations in the MAP Kinase-Related Pathways in the Brains of Mice that Display Increased Aggressiveness

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 (po0.05) decreases in MEK1, Erk2p, GSK3a, 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 GSK3a 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. Neuropsychopharmacology (2006) 31, 956-966.

Violence among Street-Involved Youth: The Role of Methamphetamine

“…One study in which mice were randomized to a chronic MA, acute MA, or control group revealed increased aggression in the chronic MA group. The authors further found evidence suggesting that such aggression may be due to disruption of the prefrontostriatal tracts, consistent with previous research in this area [9] . Another study comparing MA-dependent individuals with healthy controls found hyperactivity in the dorsal anterior cingulate cortex on functional magnetic resonance imaging and high self-ratings of hostility and interpersonal sensitivity in the MA group when exposed to fearful and angry faces [10] .…”

Ibudilast reverses the decrease in the synaptic signaling protein phosphatidylethanolamine-binding protein 1 (PEBP1) produced by chronic methamphetamine intake in rats

“…The MAPK signaling pathway has been shown to regulate behavioral sensitization and addictive properties of drugs of abuse (Licata and Pierce, 2003;Sokolov and Cadet, 2006). In a recent study, Yan et al (2014) demonstrated that the casein kinase 2-inhibitor luteolin inhibited behavioral sensitization by blocking methamphetamine-induced MAPK activation in the caudate putamen of mice.…”

The rewarding effect of aggression is reduced by nucleus accumbens dopamine receptor antagonism in mice

“…Experiments increasing extracellular levels of DA result in increased aggression, while the administration of DA antagonists decrease aggression (Kudryavtseva et al 1999;Sokolov and Cadet 2006). DA receptor knockout systems have also shown a reduced aggressive phenotype (Drago et al 1998;Miczek et al 2001).…”