Effect of Neonatal Serotonin Depletion on Morphine-, Nefopam-, Indomethacin-, and Imipramine-Induced Analgesia in Tests of Thermal and Mechanical Pain in Adult Rats

Background. Previous studies have demonstrated that chemical lesion of the noradrenergic system modified the antinociceptive effects of morphine, paracetamol, and nefopam in rats. Furthermore, it has been demonstrated that the serotoninergic as well as the noradrenergic system participate in the central effect of these drugs in different ways. Objectives. In this study the impact of serotoninergic system lesion on the antinociceptive effects of morphine, nefopam, indomethacin, and imipramine in rats was investigated. Material and Methods. Three days after birth, control rats were pretreated with desipramine HCl (20 mg/kg i.p., base) 30 min before intraventricular (i.c.v.) saline (0.85%)-ascorbic acid (0.1% a.a.) vehicle injection. A separate group received 5.7-dihydroxytryptamine (5,7-DHT; 70 μg in each lateral ventricle, base). When the rats attained 10 weeks of age, painful reactions were assessed by means of tail immersion and paw pressure tests. Furthermore, monoamines and their metabolite levels in some parts of the brain were determined using the HPLC/ED method. Results. In the tail immersion test (thermal stimulus), no differences were found in the antinociceptive actions of morphine (5.0 mg/kg s.c.), nefopam (20 mg/kg i.p.), indomethacin (5 mg/kg i.p.), and imipramine (10 mg/kg i.p.) between the control and 5,7-DHT lesioned rats. In the paw pressure test (mechanical stimulus), all the examined drugs also showed a similar analgesic effect. Biochemical studies demonstrated that in the 5,7-DHT pretreated rats there was a marked decrease in serotonin (5-HT) and 5-hydroxyindoloacetic acid (5-HIAA) levels in all the examined structures (prefrontal cortex, thalamus, and spinal cord) compared with the control group (p < 0.05). Simultaneously, no changes in noradrenalin (NA) and dopamine (DA) concentrations were observed. Conclusions. The analgesic activities of the morphine, nefopam, indomethacin, and imipramine are not perturbed by central serotoninergic system dysfunction (Adv Clin Exp Med 2010, 19, 1, 33–41).