Effects of selective estrogen receptor alpha and beta modulators on prepulse inhibition in male mice
- Journal Article
Rights / licenseIn Copyright - Non-Commercial Use Permitted
Rationale Multiple lines of evidence suggest that the sex steroid hormone 17-β estradiol (E2) plays a protective role in schizophrenia. Systemic E2 enhances prepulse inhibition (PPI) of the acoustic startle reflex, an operational measure of sensorimotor gating known to be impaired in schizophrenia and related disorders. However, the relative contribution of different estrogen-receptor (ER) isoforms in these associations still awaits examination. Objectives The present study explored the effects of ER-α and ER-β stimulation or blockade on PPI and their functional relevance in an amphetamine-induced PPI deficiency model in male mice. Methods Prior to the assessment of PPI, C57BL/6N male mice were injected with the ER-α agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), the ER-α antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1N-pyrozole dihydrochloride (MPP), the ER-β agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN), or the ER-β antagonist 4-[2-phenyl-5,7-bis (trifluoromethyl) pyrazolo [1,5-a] pyrimidin-3-yl] phenol (PHTPP), with or without concomitant amphetamine treatment. Results Acute pharmacological stimulation and blockade of ER-α, respectively, led to a dose-dependent increase and decrease in basal PPI. In contrast, acute treatment with preferential ER-β modulators spared PPI under basal conditions. Pretreatment with either ER-α or ER-β agonist was, however, effective in blocking amphetamine-induced PPI disruption. Conclusions Our study demonstrates that activation of either ER isoform is capable of modulating dopamine-dependent PPI levels. At the same time, our results suggest that endogenous ER-α signaling may be more relevant than ER-β in the regulation of sensorimotor gating under basal conditions. Show more
Journal / seriesPsychopharmacology
Pages / Article No.
SubjectAmphetamine; Dopamine; Estradiol; Estrogen; Prepulse inhibition; Schizophrenia; Sensorimotor gating
Organisational unit03274 - Langhans, Wolfgang (emeritus)
NotesIt was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
MoreShow all metadata