Serotonergic effect on cerebrospinal fluid production

Abstract

Many details concerning CSF production at the choroid plexus remain unsettled, and the control mechanisms for production are also not yet clarified. In the present study, the association of serotonin in the dynamics of CSF production was studied. The authors used the ventriculocisternal perfusion method developed by Pappenheimer and an automatic continuous measurements technique devised by the authors. The experimental animals were 48 mongrel dogs weighing 7.0 to 12.0 kg. The animals were inactivated by intravenous injection of Dialferin® after intratracheal intubation for generalized anesthesia with N2O, O2 and Halothane®. Within about 2-2.5 hours after starting perfusion of the Blue Dextran-Elliott-B perfusion fluid, the optical density reached a plateau, and the CSF production in the control dogs could be calculated. Once the data for the control had been obtained, intravenous administration of 5-hydroxytryptophan (5-HTP), noradrenaline (NA) and acetazolamide (Diamox®) was commenced. Administration of various amounts of 5-HTP, a precursor of serotonin, reduced the CSF production. After administration of 10 mg/kg, 20 mg/kg, and 30 mg/kg 5-HTP the CSF production was reduced by 37.0 ± 4.4%, 39.9 ± 3.1%, and 35.2 ± 5.5% (mean ± SD), respectively, and no correlation with dose was observed. After administration of 5-HTP, the blood pressure showed an unsteady state for about 10 minutes, with an increase in pulse pressure. It then declined gradually. All these phenomena were within the range of autoregulation. Intravenous drop infusion of noradrenaline (10-7 M) was continued, and, while monitoring blood pressure, the systolic pressure was controlled so as to maintain it at 160-180 mmHg. After administration, a decrease in CSF production of 13.8 ± 4.2% was observed. After administration of 50 mg/kg and 100 mg/kg Diamox®, the CSF production decreased by 28.5 ± 3.6%, and 57.2 ± 7.0%, respectively. Examination of the blood concentrations of adrenaline, noradrenaline and serotonin revealed the well-corresponding changes of CSF production with that of serotonin rather than adrenaline and noradrenaline after administration of 5-HTP. From these facts the serotonergic reducing effect on CSF production is proposed and the existence of serotonergic receptors is suggested. The serotonergic reducing effect corresponds to that of noradrenaline and of acetazolamide. The reducing mechanism of serotonin has not been clarified; however, a similar mechanism to that of noradrenaline which has been reported to reduce the carbonic anhydrase activity in the choroid plexus, is presumed.