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Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F, Garattini S.
“m-Chlorophenylpiperazine: A Central Serotonin Agonist Causing Powerful Anorexia in Rats”.
Naunyn-Schmiedeberg's Arch.Pharmacol.. 1979;308(2):159-63.
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Abstract
The influence of m-chlorophenylpiperazine (mCPP) on anorexia in rats was studied. Methods The uptake of dopamine (DA) by purified synaptosomes from pooled striate end uptake of noradrenaline (NA) and 5-HT by whole brain homogenates were studied. Binding of 38-5-HT was studied in a telencephalon (striate excluded) membrane preparation. Electrolytic lesions to the ventral noradrenergic bundle (VNB) and median raphe nucleus (MR) were produced in some rats. Controls were sham operated. Another group of animals were given 200 mcg 6-hydroxydopamine (6-OHDA, Roche) intraventricularly. This was preceeded 30 min earlier by 50 mg/ kg i.p pargyline. All the animals were used 12-15 days later when the effect of mCPP (1.25-5 mg/kg i.p. Angelini) on food intake was studied. Results mCPP inhibited 5-HT and NA uptake by synaptosomes uptake of DA was less affected At concentrations ranging 10^6 -10^5 M, d-amphetamine (Recordati) and d-fenfluramine (Servier) markedly increased the release of DA and that of NA and 5-HT respectively, but mCPP had little effect on monoamine release. mCPP potently displaced 3H-5-HT binding to brain membranes, as compared with displacement of a-LSD (Sandoz) and cyproheptadine (Merck-USA). mCPP produced a dose-dependent reduction in food intake, this effect was prevented by pretreatment with methergoline 1 mg/kg i.p. (Farmitalia). The effect of mCPP was unchanged in animals lesioned in the MR or those treated with 6-OHDA, and was enhanced in animals with lesions to the VNB. Neither penfluridol 2.5 mg/kg p.o. (Janssen), phentolamine 5 mg/kg i.p. (CIBA-Geigy) nor propranolol 5 mg/kg i.p. (Icpharma) modified significantly the effect of mCPP on food intake. Conclusion The decrease of food intake induced by mCPP depends on its ability to act as a serotonin agonist in the brain. rnCPP could prove an important tool in studies elucidating the functional role of serotonin in the CNS.
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