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.