Table 2.

Selected animal studies analyzing the relationship between testosterone and depression.

Species	Strain	Gender	Timing	Intervention	Maze	Mechanism	Outcome	References
Mus musculus	129:C57BL/6J	Females	Perinatal	Testosterone administered sc at 1st postnatal day; OVX at 28th postnatal day with testosterone capsule insertion	Tail ST	Organizational or activational effect	↑ immobility time in intact and all testosterone groups (depressive effect of testosterone)	Goel and Bale, 2008
Rattus norwegicus	Wistar	Males	Young adults	Testosterone application 15 min before testing in 3 doses (1, 2, 4 mg/kg)	FST	Observational	Failed to confirm main group effect of TST for immobility; 2 and 4 mg/kg groups spent less time immobile during 2nd trial (antidepressant effect)	Buddenberg et al., 2009
Mus musculus	SAMP10 SAMR1	Males	28–34 weeks	No intervention	Tail ST	Observation	SAMP10 prolongation in immobility time of tail suspension in comparison to SAMR1; SAMP10 showed lower TST levels but not DHEA; SAMR1 and SAMP10 showed significant correlation of TST and immobility; r= −0,667	Egashira et al., 2010
Mus musculus	C57/BL6	Males and Females	24 months (range 20–28)	Intact aged mice; 1 h before testing 1 mg/kg of TST, E2, DHT, or 3-alpha diol administered sc	FST	Observational	Main effect of sex and androgen for immobility; Aged male ↑ time immobile compared to other male groups; Aged female mice were less immobile than aged male mice (antidepressive effect of androgens and E2)	Frye and Walf, 2009
Rattus norwegicus	Sprague-Dawley	Young adults	Males and females	Gonadectomy in adulthood; Females masculinized by TP at PD 1	Learned helplessness Avoidance test Tested in adulthood	Observational/mechanism either TST or E2 organization/activation effect	All Males not able to learn to escape stress during training; all females learned to escape; TST and metabolites from periphery did not influence depressive behavior through organizational effect	Dalla et al., 2008
Mus musculus	C17/BL6	Males	8–10 weeks	ArKO mice and null KO	FST	Mechanism—through AR receptor?	ArKO did not differ in FST; ArKO exhibited normal levels of motor activity, anxiety and depression; CUMS had no effect	Dalla et al., 2005
Rattus norwegicus	Wistar	Males and females	Prepubertal and young adult males and females in estrus	No intervention	FST	Observation	Prepubertal rats of both sex increased immobility, adult males higher immobility than adult females; (depressive effect of testosterone)	Martinez-Mota et al., 2011
Rattus norwegicus	Wistar	Males and females	Young adults and 12–15 months adult rats	Gonadectomy in younger TST containing pellets in older animals	Anhedonic test CUMS		TST before CUMS prevented anhedonia in older rats; in young, gonadectomy did not increase vulnerability to anhedonia	Herrera-Perez et al., 2012
Rattus norwegicus	Sprague-Dawley	Males and females	Young adults	Gonadectomy, with pellet of TST or imipramine	Anehodonia test Novelty induced hypophagia	Observational	Testosterone had anxiolytic and antidepressant effect in males but not in OVX females; same effect as imipramine	Carrier and Kabbaj, 2012

FST, forced swim test; CUMS, chronic unpredictable mild stress; Tail ST, tail suspension test; TST, testosterone; TP, testosterone propionate; E2, estradiol; DHEA, dehydroepiandrosterone; SAMP, senescent prone mice; SAMR, senescent resistant mice; ArKO, androgen receptor knock-out; PD, postnatal day; sc, subcutaneously.