Chronic mianserin or eltoprazine treatment in rats: effects on the elevated plus-maze test and on limbic 5-HT2C receptor levels.
Rats were chronically treated with mianserin (10 mg/kg i.p.) or eltoprazine (1 mg/kg i.p.) and were tested in the elevated plus-maze test for anxiety. 5-HT2C (previously 5-HT1C, see Humphrey et al., 1993, Trends Pharmacol. Sci. 14, 223) binding sites and their mRNA were evaluated in limbic structures (i.e., amygdala, hippocampus, septum) of a sample of these rats by autoradiographic binding studies and in situ hybridization histochemistry. Mianserin and eltoprazine displayed opposite effects in the elevated plus-maze: mianserin induced anxiolytic-like effects, while eltoprazine showed anxiogenic-like ones. Within the amygdala, but not in other structures, the quantitative autoradiographic analysis of the 5-HT2C binding sites showed a differential effect: mianserin treatment induced a decrease in the number of these sites, while eltoprazine treatment resulted in an increase. In spite of this, neither mianserin- nor eltoprazine-treated rats displayed an alteration in the 5-HT2C receptor mRNA levels in the brain regions examined. Our results are suggestive of a relation between anxiolytic/anxiogenic-like effects and the level of 5-HT2C binding sites in the amygdala.
Rocha
B
B
Laboratoire de Neurophysiologie et Biologie des Comportements, Strasbourg, France.
Rigo
M
M
Di Scala
G
G
Sandner
G
G
Hoyer
D
D
D000110:Acetylcholinesterase / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D005629:Frozen Sections; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006651:Histocytochemistry; D017403:In Situ Hybridization; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008803:Mianserin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012686:Septal Nuclei / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D010879:Piperazines; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D008803:Mianserin; C063828:eltoprazine; D000110:Acetylcholinesterase