The effect of BIMT 17, a new potential antidepressant, in the forced swimming test in mice.
BIMT 17 inhibits cortical electrical activity through the activation of cortical 5-HT(1A) receptors combined with the antagonism of 5-HT(2) receptors. The aim of this study was to evaluate the potential antidepressant activity of BIMT 17 and its mechanism of action by using the forced swimming test in mice. BIMT 17, when administered i.p. (16mg/kg), s.c. (8mg/kg) and orally (32mg/kg), increased the struggling time in mice forced to swim. With i.p. administration, BIMT 17 did not alter locomotor activity. The effect of BIMT 17 seems to be mediated by 5-HT(1A) receptors since it was antagonised by WAY 100135 (10mg/kg i.p.), a selective 5-HT(1A) antagonist. The 5-HT(2) component does not seem to modulate BIMT 17 activity since the administration of DOI (1mg/kg i.p.), a 5-HT(2A/2C) agonist, did not modify the BIMT 17 effect. Antagonism of BIMT 17 was also produced by buspirone (30mg/kg p.o.), alpha-methyl-p-tyrosine (250mg/kg i.p.) and sulpiride (50mg/kg i.p.) but not by pindolol (20mg/kg i.p.). Neither the reduction of 5-HT synthesis brought about by p-chlorophenylalanine nor the selective destruction of 5-HT containing neurons by 5,7-dihydroxytryptamine reduced the BIMT 17 effect, suggesting that BIMT 17 acts postsynaptically in increasing struggling behaviour.
Department of Pharmacology, Boehringer Ingelheim Italia S.p.A., Via Lorenzini 8, 20139 Milano, Italy.
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Cesana
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Ciprandi
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Borsini