Sex-related effects of agmatine on caffeine-induced locomotor activity in Swiss Webster mice

Abstract

In mammalian brain, agmatine is an endogenous amine that is synthesized through the decarboxylation of l-arginine by arginine decarboxylase. It has been proposed as a new neurotransmitter and/or neuromodulator. It was shown that agmatine had some beneficial effects in animal models of opioid and alcohol addiction. Locomotor stimulant properties of drugs such as ethanol, caffeine, nicotine and amphetamine have been linked to their addictive properties. The present study investigates the effects of agmatine on caffeine-induced locomotor activity both in male and female mice. Adult Swiss Webster mice were used in the study. Locomotor activity was measured for 30 min immediately following caffeine (2.5, 5, 10 and 20 mg/kg, i.p.) or saline treatments. Agmatine (5, 10 and 20 mg/kg, i.p.) were injected 20 min before caffeine (2.5 and 5 mg/kg, i.p.) administration. In both sexes, agmatine (5–20 mg/kg) were also tested for ability to depress or stimulate locomotor activity in the absence of caffeine. Caffeine (5 mg/kg) induced a significant increase in locomotor activity of both male and female mice. There was no significant difference in the locomotor-activating effects of caffeine between male and female mice. Agmatine blocked the caffeine (5 mg/kg)-induced locomotor stimulation dose dependently in male but not female mice. Agmatine had not any effect on the lower dose (2.5 mg/kg) of caffeine in both sexes. These results suggest that agmatine has sex-related inhibitory effects on caffeine-induced locomotor activity in Swiss Webster mice, and male mice are more sensitive than the females to the effect of agmatine.