title: Specificity and efficacy of noradrenaline, serotonin depletion in discrete brain areas of Swiss mice by neurotoxins.
abstract: The aim of this work is to define neurotoxins doses to have efficient and specific depletion of noradrenaline (NA), serotonin (5-HT) neurotransmission in cortex, striatum, hippocampus and hypothalamus of Swiss mice after intraperitoneal administration of, respectively, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) and para-chlorophenylalanine methyl ester hydrochloride (PCPA). The neurotransmitters concentrations were determined by high performance liquid chromatography with amperometric detection. The minimal single dose necessary to produce a highly significant decrease of NA levels (p<0.01 in comparison with control group) in hypothalamus (-44%), hippocampus (-91%), striatum (-40%) and cortex (-68%) was 50mg/kg but DA and 5-HT levels were modified, respectively, in hypothalamus and striatum. Three doses of PCPA 300 mg/kg over 3 consecutive days involve a profound depletion of 5-HT transmission in all discrete brain areas but NA and DA levels were also significantly reduced. In conclusion, DSP-4 has a different efficacy in discrete brain areas with a noradrenergic specificity which is not absolute, PCPA has a similar efficacy in all brain areas but is unspecific of 5-HT transmission.
authors.affiliation: EA Neurobiologie de l'Anxiété et la Dépression, Faculté de Médecine de Nantes, Laboratoire de Pharmacologie Clinique, Institut de Biologie, Centre Hospitalier Universitaire, 9 quai Moncousu, 44093 Nantes Cedex 1, France. eric.dailly@chu-nantes.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Franck
authors.initials: F
authors.lastname: Chenu
authors.forename: Benoit
authors.initials: B
authors.lastname: Petit-Demoulière
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D009498:Neurotoxins; D014179:Neurotransmitter Uptake Inhibitors; C020261:4-chlorophenylalanine methyl ester; D012701:Serotonin; C012102:DSP 4; D010134:Fenclonine; D009638:Norepinephrine