Introduction. Many known substances affecting the serotoninergic system induce definite physiological effects, including those which are therapeutic. For instance, the enhanced serotoninergic transmission due to decreased functions of autoreceptors and increased inhibitory functions of postsynaptic 5-HT1A is associated with antidepressant effect. The central serotoninergic system takes part in the regulation of many bodily functions, such as sleep, wakefulness, blood pressure, pain perception or sexual behaviours. Moreover, it is involved in the pathogenesis of depression, anxiety, addictions, migraine and other headaches. In pain therapy, not only typical analgesics are used, but also substances without obvious analgesic effect, thus allowing potential pharmacological modulation of analgesic activity in the treatment of pain. Objective. The aim of the study was to determine whether a chemical lesion to the central noradrenergic system at an early stage of individual development alters reactivity of 5-HT3 receptors in adult rats. Materials and method. The study used newborn and adult Wistar rats aged 8–10 weeks. Behavioural tests (writhing test, formalin assay) were used to assess the analgesic action of ondansetron as a 5-HT3 receptor antagonist. Results. The analgesic effect of ondansetron (1.0 mg/kg b.w., i.p.) in the writhing test was weak and short. Pain intensity score after ondansetron injection (1.0 mg/kg b.w., i.p) was 2–3 points and did not differ significantly between the study groups. Conclusions. Damage to the central noradrenergic system at an early stage of individual development has no effect on the antinociceptive effects of the serotonin (5-HT3) receptor antagonist, ondansetron, in the persistent pain model.
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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.