Table 1.

Simplified summary of effects of tamoxifen on various behaviors and neuropsychiatric functions in both humans and animals according to hormonal status and the hypothesized mechanism.

Neuropsychiatric function/behavior	Species	Hormonal status	Tamoxifen effects	Proposed mechanism	References
Cognition	Mice, Rats	Intact adult males and females	Impaired working memory and object recognition	Antiestrogen	Chen et al., 2002; Walker et al., 2011; Valvassori et al., 2017a, 2017b
	Mice, Rats	Ovariectomized and aged intact females	Improved working memory and spatial memory	Estrogen mimetic	Velázquez-Zamora et al., 2012; Pandey et al., 2016
	Humans	Premenopausal and postmenopausal females	Impaired verbal memory	Antiestrogen	Schilder et al., 2010; Castellon et al., 2004; Bender et al., 2006; Boele et al., 2015; Chen et al., 2014.
Depressive-like behavior	Rats	Intact adult females	Increased immobility in the forced swim test	Antiestrogen	Azizi-Malekabadi et al., 2015
	Mice	Ovariectomized	Decreased immobility in forced swim test	Estrogen mimetic	Calmarza-Font et al., 2012
	Humans	Premenopausal and postmenopausal females	No increase in depressive symptoms	–	Bender et al., 2006; Day et al., 2001; Lee et al., 2007
Anxiety-like behavior	Mice, Rats	Intact adult males and females	Decreased exploration in elevated plus maze	Antiestrogen	Li et al., 2019; Azizi-Malekabadi et al., 2015
	Mice, Rats	Ovariectomized	Increased exploration in elevated plus maze	Estrogen mimetic	Azizi-Malekabadi et al., 2015; Calmarza-Font et al., 2012
	Human	Premenopausal andpostmenopausal Females	No effect	–	Biro et al., 2019; Boele et al., 2015; Marianne Nystedt et al.,2000
Mania	Mice, Rats	Intact adult males and females	Reduction in induced hyperlocomotion	Protein kinase C inhibition	Abrial et al., 2014; Armani et al., 2012; Einat et al., 2007; Sabioni et al., 2008; Valvassori et al., 2017a, 2017b
	Humans	Males and females (all ages)	Decreased mania per standardized rating scales	Protein kinase C inhibition	Amrollahi et al., 2011; Bebchuk et al., 2000; Kulkarni et al., 2014; Palacios et al., 2019; Yildiz et al., 2016; Zarate et al., 2007
Psychosis	Rats	Ovariectomized females	Restoration of deficient sensory gating (Pre-pulse inhibition) induced by dopaminergic stimulation	Estrogen mimetic	Gogos & van den Buuse, 2015; Sbisa et al., 2018
Substance use	Rats	Intact males	Decreased amphetamine-induced dopamine efflux and decreased self-administration (tamoxifen analog)	Dopamine transporter inhibition, Protein Kinase C inhibition	Carpenter et al., 2005; Mikelman et al., 2018