Antiaggressive effects of topiramate in agonistic encounters between male mice

Abstract

Topiramate, an antiepileptic drug, has been found to be useful for the treatment of aggression in clinical populations. However, no studies have explored the action of this compound on aggressive behavior in laboratory animals. This work examined the effects of topiramate (10, 20, 40 and 80 mg/kg, i.p.) on agonistic interactions between male mice, using an ethopharmacological approach. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration. Ten minutes of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. The encounters were videotaped and the accumulated time allocated by subjects to 10 broad behavioral categories was estimated using an ethologically based analysis. Results showed that topiramate (20-80 mg/kg) produced a significant reduction of offensive behaviors (threat and attack), without affecting immobility. Digging behavior (all doses) was also significantly decreased. The antiaggressive effects of topiramate could be related to its ability for modulating positively GABA-A receptors and/or blocking AMPA subtype of glutamate receptors.

Acute topiramate differentially affects human aggressive responding at low vs. moderate doses in subjects with histories of substance abuse and antisocial behavior

“…Several GABA-modulating drugs, in particular those used as antiepileptics, have shown promise as anti-aggressive agents in both non-humans (Navaro et al, 2007; Rogers and Depaulis, 1982) and humans who are at higher than normal risk for aggressive behavior (Guay 2007; Stanford et al, 2005; Nickel and Loew, 2008). It has been suggested that the mechanism for these anti-aggressive effects may be an interaction of (a) the individual organism’s history of aggressive behavior and (b) available levels of CNS GABA, which putatively serve an inhibitory function in modulating other receptor systems (DA and 5-HT) and prefrontal-limbic circuits active during bouts of aggressive behavior (Bjork, 2001; Miczek et al, 2003; Siever, 2008).…”

Dopamine receptors in emesis: Molecular mechanisms and potential therapeutic function

“…-Higher doses (e.g. 0.8 mg/kg) produce a significant elevation in defense/submission, avoidance/fleeing, and social investigation behaviors [276].…”

Acute administration of a dopamine D2/D3 receptor agonist alters behavioral and neural parameters in adult zebrafish

“…Quinpirole administration has been used in rats and mice to model psychiatric disorders, such as obsessive-compulsive disorder and schizophrenia. After exposure, the animals presented anxiety-like behavior and elevated stereotypic and erratic movements (Hoffman, 2011;Kostrzewa et al, 2016;Navarro & Maldonado, 1999;Nielsen et al, 2017;Sams-Dodd, 1998;Szechtman et al, 2017). Additionally, only a few studies have reported alterations in social and aggressive behavior (Maple et al, 2017;Sams-Dodd, 1998;Szechtman et al, 2017).…”