Inhibitory effects of clonidine on serotonergic neuronal activity as measured by cerebrospinal fluid serotonin and its metabolite in anesthetized rats.

Clonidine-induced changes in the serotonergic neuronal activity of the central nervous system were estimated by measuring the concentrations of serotonin (5-HT) and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in the cerebrospinal fluid (CSF) of anesthetized rats. Clonidine (30 and 300 micrograms/kg, i.v.) led to 74% and 60% reductions in the concentration of 5-HT in the CSF 60 min after administration. CSF 5-HIAA concentrations were also decreased to 77% and 66%, respectively. Clonidine-induced (30 micrograms/kg, i.v.) decreases in CSF 5-HT and 5-HIAA concentrations were attenuated by pretreatment with idazoxan (5 mg/kg, i.p.). Idazoxan by itself did not alter the CSF 5-HT and 5-HIAA concentrations. Decreased CSF 5-HT and 5-HIAA concentrations after i.v. administration of clonidine (30 micrograms/kg) were abolished by noradrenergic denervation after pretreatment with 6-hydroxydopamine (200 micrograms/rat, i.c.v.). These results suggest the possibility that clonidine acts to inhibit the serotonergic neuronal activity, which is mediated via the alpha 2-adrenoceptors. It indicates, moreover, that noradrenergic nervous systems are involved in the clonidine-induced inhibition of serotonergic neuronal activity. Therefore, noradrenergic neurons play a significant role in mediating the actions of clonidine on serotonergic neuronal activity in the rat brain.