Nicotine antagonizes the effects of reserpine on the striatal metabolism of dopamine, 5-hydroxytryptamine and noradrenaline in hypothermic but not in normothermic mice

Summary

Our previous studies indicate that repeated nicotine administration inhibits the release of striatal dopamine in hypothermic mice. To study if similar inhibition occurs in noradrenergic and serotoninergic neurons mice were given (−)-nicotine (3 mg/kg, s.c.) repeatedly at 110, 80, 50, and 20 min before sacrifice. The interactions of nicotine with reserpine were also investigated. Reserpine (5 mg/kg, i.p.) was administered after the second nicotine dose at 60 min before sacrifice. To prevent the effects of nicotine on autonomic ganglia all mice were given hexamethonium (10 mg/kg, i.p.). Experiments were carried out at 20–22°C at which ambient temperature nicotine induced deep hypothermia or at 32–34°C to prevent the drug-induced hypothermia. The changes in striatal metabolism of dopamine, noradrenaline and 5-hydroxytryptamine (5-HT) we

Nicotine had temperature dependent effects on the dopamine metabolism which indicates a block of dopaminergic neurons as suggested in our earlier studies. Reserpine per se increased the homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents and decreased the 3-methoxytyramine (3-MT) and dopamine contents at both ambient temperatures. In hypothermic but not in “normothermic”, nicotine-treated mice reserpine's effect on dopamine metabolism was almost totally vanished. Nicotine and reserpine per se increased the 3-methoxy-4-hydroxyphenylethylglycol (MOPEG) content and decreased the noradrenaline content at both ambient temperatures. In hypothermic but not in “normothermic” mice nicotine antagonized the reserpine-induced decrease of noradrenaline content. Nicotine tended to decrease the 5-hydroxy-indoleacetic acid (5-HIAA) content in hypothermic mice but increased it in “normothermic” ones. Reserpine decreased the 5-HT content and increased the 5-HIAA content at both ambient temperatures. In hypothermic but not in “normothermic”, nicotine-treated mice the reserpine-induced effects on 5-HT metabolism were clearly reduced. These results indicate that in hypothermic mice repeatedly administered nicotine blocks the release of striatal dopamine and 5-HT and perhaps also noradrenaline. The nicotine-induced antagonism of the effects of reserpine is temperature-dependent as the nicotine-induced blockade of the neurons and thus the main mechanism behind both of these phenomena could be the sustained depolarization of the monoaminergic neurons.