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Gallager DW, Aghajanian GK. 
“Inhibition of Firing of Raphe Neurones by Tryptophan and 5-Hydroxytryptophan: Blockade by Inhibiting Serotonin Synthesis with Ro-4-4602”. 
Neuropharmacology. 1976;15(3):149-156.
The effect of Ro-4-4602 on the inhibition of raphe neuronfiring by tryptophan and 5-hydroxytryptophan (5-HTP) was studied. Methods Electrodes were stereotaxically-implanted into the midbrain raphe area of male albino Charles River rats (220-280 g) under chlorar hydrate anesthesia. The influĆnce of tryptophan (100 mg/kg; i,p Calbiochem) on raphe neuron firing was measured in rats pretreated with either Ro-04-4602 (800 mg/kg i,p" Roche), pchlorophenylalanine (400 mg/kg, i.p Regis) or LSD (20 mcg/kg i.v.). The influence of Ro-04-4602 (800 mg/kg, ip.) on raphe firing promoted by microiontophoretically-applied 5-HTP, tryptophan or serotonin (5-HT) was also examined. Results Tryptophan (iOO mg/kg i.p.j depressed raphe cell firing within 5-10 min, this depression being completely prevented by Ro-4-4602, and LSD, but unaffected by p-chlorophenylalanine. Ro-4-4602 significantly depressed-both raphe and forebrłin 5-HT concentratiops even after:└ryptophan treatment. Microlontophoretic application of tryptophan or 5-HT depressed raphe neuron firing by 82% and 95%, respectively. Pretreatment with Ro-4-4602 significantly attenuated the inhibition of raphe neuron firing caused by microlontophoretically applied tryptophan but had no effect on the-inhibition due to 5-HT. Administration of 5-HTP (Sigma, 150 mg/kg i.p.) caused an inhibition of raphe neuron firing which was reversed by Ro-4-4602 (800 mg/kg i.p.). Microiontophoretically applied 5-HTP also inhibited raphe cell firing. Conclusion Raphe cell firing is inhibited by 5HT precursors through their enzymatic conversion to 5-HT
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