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Da Prada M, Pieri L, Keller HH, Pieri M, Bonetti EP.
“Effects of 5,6-Dihydroxytryptamine and 5,7-Dihydroxytryptamine on the Rat Central Nervous System After Intraventricular or Intracerebral Application and on Blood Platelets In Vitro”.
Ann.N.Y.Acad.Sci.. 1978;305:595-620.
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Abstract
The effects of 5,6-dihydroxytryptamine (5,6-DHT) and 5,7 dibydroxytryptamine (5,7-DHT) on the rat central nervous system after intraventricular (ivt) or intracerebral (icy) application and on blood platelets in vitro were studied. The creatinine sulfate saps of 5,7-DHT (50 mcg of base) and 5,7-DHT (75 mcg of base, Regis) were injected into the right lateral cerebral ventricle of rats. In some studies, injection of 5,7-DHT was preceded for various periods of time by an i.p. injection of desmethylimipramine (DMI), maprotiline, Lu 10-17t, or harmaline. Injection of both 5,6-DHT and 5,7-DHT (the latter under protection of specific noradrenaline (NA) uptake blockers) icv induced a marked decrease of cerebral 5-HT levels, without significantly changing catecholamine (CA) levels. Lu 10-171 prevented a major uptake of 5,7-DHT into 5-HT neurons, but did not alter the neurotoxic effect on dopamine (DA) and NA neurons. Harmaline reduced the neurotoxicity of 5,7-DHT for CA neurons. When injected stereotaxically into the medial forebrain bundle (MFB), 5,6-DHT markedly and 5,7-DHT slightly decreased cerebral levels of DA, in addition to those of 5-HT. After icv or local injection in the MFB, 5,7-DHT reduced not only 5-hydroxyindoleacetic acid (5-H[AA) but also homovanillic acid (HVA) levels. In rats lesioned with 5,7-DHT, the enhancement of 5-HT and DA turnover induced by methiothepin was markedly reduced. 3-Methoxy-4-hydroxypkenylethyleneglycol sulfate (MOPEG-SO4) was moderately increased in rats injected with 5,7-DHT icy. Changes in amine metabolites appeared to better reflect the extension of damage to monoaminergic neurons than alterations of the concentrations of the amines themselves. Enhancement of mounting activity, similar to that seen after systemic injection of p-chlorophenylalanine (p-CPA), was induced by icv 5,6-DHT and 5,7-DHT in intact adult male and female rats and in castrated, ovariectomized, or prepubertal rats. Brain 5-HT levels were reduced. Injection of 5-HT or haloperidol suppressed enhanced sexual activity. Lisuride (Lysenyl, Spofa), d-LSD, piribedil, ergometrine, ergocornine and apomorphine induced contralateral turning behavior in rats injected with 5,6-DHT in one MFB, blocked by neuroleptics while methylphenidate and methamphetamine induced ipsilateral turning. Electron microscopic studies showed that 5,6-DHT, 5,7-DHT and etaraminol accumulate in rat platelets, with release of 5-HT.
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