Effects of serotine receptors agonists, TFMPP and CGS12066B, on regional serotonin synthesis in the rat brain: an autoradiographic study.
The effects of acute and repeat administration of the serotonin (5-HT)(1) agonists TFMPP [N -(3-trifluoromethyl)phenylpiperazine hydrochloride] and CGS12066B [7-trifluoromethyl-4- (4-methyl-1-piperazinyl)pyrrolo[1,2-a ]-quinoxaline dimaleate] were evaluated on 5-HT synthesis rates using the alpha-[(14) C]methyl-l-tryptophan (alpha-MTrp) autoradiographic method. In the acute treatment study, TFMPP (10 mg/kg) and CGS12066B (5 mg/kg) were injected intraperitoneally 30 min before an alpha-MTrp injection. In an acute study TFMPP reduced overall brain 5-HT synthesis, in the dorsal and median raphe, and in almost all of their projection areas, with the exception of the parietal, sensory-motor, and frontal cortices, the accumbens nucleus, and the caudate. Acute CGS12066B treatment did not have overall significant effect, but the rates did decrease in the cell body areas of 5-HT neurons. In a 7-day treatment with TFMPP (10 mg/kg/day) or CGS12066B (5 mg/kg/day), the 5-HT synthesis rates (24 h after last dose) decrease, with both compounds, in almost all of the nerve terminal structures. TFMPP reduced the synthesis in the dorsal and median raphe, while CGS12066B reduced it only in the dorsal raphe. This data suggests that after a 7-day treatment with TFMPP and CGS12066B, the rate of 5-HT synthesis in the dorsal raphe is restored and is reduced in many projection areas. The observed effects in the 7-day treatment could also be related to actions through the postsynaptic 5-HT(1B) sites and/or other 5-HT receptors since this compounds have limited selectivity.
Tohyama
Yoshihiro
Y
Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Yamane
Fumitaka
F
Fikre Merid
Maraki
M
Blier
Pierre
P
Diksic
Mirko
M
D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D007274:Injections, Intraperitoneal; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014018:Tissue Distribution; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism
D002250:Carbon Radioisotopes; D010879:Piperazines; D011810:Quinoxalines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C052561:CGS 12066B; C020774:alpha-methyltryptophan; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D014364:Tryptophan