Involvement of some 5-HT receptors in methamphetamine-induced locomotor activity in mice

Effects of some selective 5-HT antagonists on methamphetamine-induced locomotor activity were investigated in male mice in order to study whether this effect of methamphetamine is selectively or at least partially, induced through stimulation of a specific serotonin receptor subtype. Methamphetamine (1.5mg/kg, IP) produced a significant increase in locomotor activity. Methamphetamine-induced hyperactivity by the above mentioned dose was signficantly antagonized by NAN-190 ( 5-HT1A antagonist) at a dose of 4 mg/kg, IP, methiothepin (5-HT1B/1D antagonist) at a dose of 0.1mg/kg, IP or mianserin ( 5-HT2C antagonist) at a dose of 8mg/kg, IP. On the other hand, methysergide ( 5-HT 2A/2B antagonist) at a dose of 1mg/kg, IP or ondansetron ( 5-HT3 antagonist) at a dose of 0.5mg/kg, IP potentiated the methamphetamine-induced hyperactivity. None of the above mentioned doses of 5-HT antagonists altered the spontaneous activity of mice when administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the locomotor stimulant activity of methamphetamine in mice. This role is possibly mediated through direct stimulation of some 5-HT receptor subtypes. Stimulation by methamphetamine of 5-HT 1A, 5-HT 1B/1D and/or 5-HT2C receptor subtypes may result in hyperactivity, whereas stimulation by methamphetamine of 5-HT 2A/2B and/or 5-HT3 receptor subtypes may result in decreased activity.