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Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats

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Abstract

Rationale

Allopregnanolone is a neurosteroid involved in depression, memory, social, and sexual behavior. We have previously demonstrated that treatment with a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds frequently used in hormonal contraception, decreased brain allopregnanolone concentrations. These changes may contribute to some of the emotional and sexual disorders observed in hormonal contraceptive users.

Objectives

We thus examined whether the reduction in allopregnanolone concentrations induced by long-term EE/LNG administration was associated with altered emotional, learning, social, and sexual behaviors.

Methods

Rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to behavioral tests 24 h after the last administration.

Results

EE/LNG treatment reduced immobility behavior in the forced swim test, without affecting sucrose preference and spatial learning and memory. In the resident–intruder test, EE/LNG-treated rats displayed a decrease in dominant behaviors associated with a reduction in social investigation. In the paced mating test, EE/LNG treated rats showed a reduction in proceptive behaviors, while the lordosis quotient was not affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats increased sexual activity and cerebrocortical allopregnanolone concentrations. Prior administration of finasteride decreased allopregnanolone concentrations and abolished the increase in proceptivity induced by progesterone administration.

Conclusions

The decrease in brain allopregnanolone concentrations induced by EE/LNG treatment is associated with a reduction in social behavior and sexual motivation in female rats. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.

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References

  • Archer J (2006) Testosterone and human aggression: an evaluation of the challenge hypothesis. Neurosci Biobehav Rev 30:319–345

    Article  CAS  PubMed  Google Scholar 

  • Battaglia C, Battaglia B, Mancini F, Busacchi P, Paganotto MC, Morotti E, Venturoli S (2012) Sexual behavior and oral contraception: a pilot study. J Sex Med 9:550–557

    Article  CAS  PubMed  Google Scholar 

  • Baum MJ (1983) Hormonal modulation of sexuality in female primates. Bioscience 33:578–582

    Article  Google Scholar 

  • Bottcher B, Radenbach K, Wildt L, Hinney B (2012) Hormonal contraception and depression: a survey of the present state of knowledge. Arch Gynecol Obstet 286:231–236

    Article  CAS  PubMed  Google Scholar 

  • Brann DW, Putnam CD, Mahesh VB (1990) Gamma-aminobutyric acidA receptors mediate 3α-hydroxy-5α-pregnan-20-one-induced gonadotropin secretion. Endocrinology 126:1854–1859

    Article  CAS  PubMed  Google Scholar 

  • Carre JM, McCormick CM, Hariri AR (2011) The social neuroendocrinology of human aggression. Psychoneuroendocrinology 36:935–944

    Article  CAS  PubMed  Google Scholar 

  • Caruso S, Agnello C, Intelisano G, Farina M, Di Mari L, Cianci A (2004) Sexual behavior of women taking low-dose oral contraceptive containing 15 microg ethinylestradiol/60 microg gestodene. Contraception 69:237–240

    Article  CAS  PubMed  Google Scholar 

  • Carver CM, Reddy DS (2013) Neurosteroid interactions with synaptic and extrasynaptic GABAA receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability. Psychopharmacology (Berl) 230:151–188

    Article  CAS  Google Scholar 

  • Chesler EJ, Juraska JM (2000) Acute administration of estrogen and progesterone impairs the acquisition of the spatial Morris water maze in ovariectomized rats. Horm Behav 38:234–242

    Article  CAS  PubMed  Google Scholar 

  • Clipperton Allen AE, Cragg CL, Wood AJ, Pfaff DW, Choleris E (2010) Agonistic behavior in males and females: effects of an estrogen receptor beta agonist in gonadectomized and gonadally intact mice. Psychoneuroendocrinology 35:1008–1022

    Article  CAS  PubMed  Google Scholar 

  • Concas A, Mostallino MC, Porcu P, Follesa P, Barbaccia ML, Trabucchi M, Purdy RH, Grisenti P, Biggio G (1998) Role of brain allopregnanolone in the plasticity of γ-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery. Proc Natl Acad Sci U S A 95:13284–13289

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Estanislau C, Ramos AC, Ferraresi PD, Costa NF, de Carvalho HM, Batistela S (2011) Individual differences in the elevated plus-maze and the forced swim test. Behav Process 86:46–51

    Article  Google Scholar 

  • Everitt BJ (1990) Sexual motivation: a neural and behavioural analysis of the mechanisms underlying appetitive and copulatory responses of male rats. Neurosci Biobehav Rev 14:217–232

    Article  CAS  PubMed  Google Scholar 

  • Fish EW, De Bold JF, Miczek KA (2002) Aggressive behavior as a reinforcer in mice: activation by allopregnanolone. Psychopharmacology (Berl) 163:459–466

    Article  CAS  Google Scholar 

  • Fish EW, Faccidomo S, DeBold JF, Miczek KA (2001) Alcohol, allopregnanolone and aggression in mice. Psychopharmacology (Berl) 153:473–483

    Article  CAS  Google Scholar 

  • Follesa P, Porcu P, Sogliano C, Cinus M, Biggio F, Mancuso L, Mostallino MC, Paoletti AM, Purdy RH, Biggio G, Concas A (2002) Changes in GABAA receptor γ2 subunit gene expression induced by long-term administration of oral contraceptives in rats. Neuropharmacology 42:325–336

    Article  CAS  PubMed  Google Scholar 

  • Frye CA (2001) The role of neurosteroids and non-genomic effects of progestins and androgens in mediating sexual receptivity of rodents. Brain Res Brain Res Rev 37:201–222

    Article  CAS  PubMed  Google Scholar 

  • Frye CA, Bayon LE, Pursnani NK, Purdy RH (1998) The neurosteroids, progesterone and 3α,5α-THP, enhance sexual motivation, receptivity, and proceptivity in female rats. Brain Res 808:72–83

    CAS  PubMed  Google Scholar 

  • Frye CA, Koonce CJ, Walf AA, Rusconi JC (2013) Motivated behaviors and levels of 3α,5α-THP in the midbrain are attenuated by knocking down expression of pregnane xenobiotic receptor in the midbrain ventral tegmental area of proestrous rats. J Sex Med 10:1692–1706

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Frye CA, Rhodes ME (2006) Infusions of 5α-pregnan-3α-ol-20-one (3α,5α-THP) to the ventral tegmental area, but not the substantia nigra, enhance exploratory, anti-anxiety, social and sexual behaviours and concomitantly increase 3α,5α-THP concentrations in the hippocampus, diencephalon and cortex of ovariectomised oestrogen-primed rats. J Neuroendocrinol 18:960–975

    Article  CAS  PubMed  Google Scholar 

  • Frye CA, Vongher JM (2001) Ventral tegmental area infusions of inhibitors of the biosynthesis and metabolism of 3α,5α-THP attenuate lordosis of hormone-primed and behavioural oestrous rats and hamsters. J Neuroendocrinol 13:1076–1086

    Article  CAS  PubMed  Google Scholar 

  • Frye CA, Wawrzycki J (2003) Effect of prenatal stress and gonadal hormone condition on depressive behaviors of female and male rats. Horm Behav 44:319–326

    Article  CAS  PubMed  Google Scholar 

  • Genazzani AR, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, Nappi RE, Luisi S, Palumbo M, Purdy RH, Luisi M (1998) Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab 83:2099–2103

    Article  CAS  PubMed  Google Scholar 

  • George O, Vallee M, Vitiello S, Le Moal M, Piazza PV, Mayo W (2010) Low brain allopregnanolone levels mediate flattened circadian activity associated with memory impairments in aged rats. Biol Psychiatry 68:956–963

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gilbert Evans SE, Ross LE, Sellers EM, Purdy RH, Romach MK (2005) 3α-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period. Gynecol Endocrinol 21:268–279

    Article  CAS  PubMed  Google Scholar 

  • Gilman DP, Hitt JC (1978) Effects of gonadal hormones on pacing of sexual contacts by female rats. Behav Biol 24:77–87

    Article  CAS  PubMed  Google Scholar 

  • Giraldi A, Marson L, Nappi R, Pfaus J, Traish AM, Vardi Y, Goldstein I (2004) Physiology of female sexual function: animal models. J Sex Med 1:237–253

    Article  CAS  PubMed  Google Scholar 

  • Girdler SS, Klatzkin R (2007) Neurosteroids in the context of stress: implications for depressive disorders. Pharmacol Ther 116:125–139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Girdler SS, Straneva PA, Light KC, Pedersen CA, Morrow AL (2001) Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric disorder. Biol Psychiatry 49:788–797

    Article  CAS  PubMed  Google Scholar 

  • Glaser JH, Etgen AM, Barfield RJ (1985) Intrahypothalamic effects of progestin agonists on estrous behavior and progestin receptor binding. Physiol Behav 34:871–877

    Article  CAS  PubMed  Google Scholar 

  • Graham CA, Bancroft J, Doll HA, Greco T, Tanner A (2007) Does oral contraceptive-induced reduction in free testosterone adversely affect the sexuality or mood of women? Psychoneuroendocrinology 32:246–255

    Article  CAS  PubMed  Google Scholar 

  • Graham CA, Ramos R, Bancroft J, Maglaya C, Farley TM (1995) The effects of steroidal contraceptives on the well-being and sexuality of women: a double-blind, placebo-controlled, two-centre study of combined and progestogen-only methods. Contraception 52:363–369

    Article  CAS  PubMed  Google Scholar 

  • Grant EC, Mackintosh JH (1963) A comparison of the social postures of some common laboratory rodents. Behaviour 21:246–259

    Article  Google Scholar 

  • Guida M, Di Spiezio SA, Bramante S, Sparice S, Acunzo G, Tommaselli GA, Di Carlo C, Pellicano M, Greco E, Nappi C (2005) Effects of two types of hormonal contraception—oral versus intravaginal—on the sexual life of women and their partners. Hum Reprod 20:1100–1106

    Article  CAS  PubMed  Google Scholar 

  • Guy AJ, Schuerch FS, Heffernan S, Thomson PC, O'Brien JK, McGreevy PD (2008) The effect of medroxyprogesterone acetate on behavioural responses of captive female hamadryas baboons (Papio hamadryas). Anim Reprod Sci 108:412–424

    Article  CAS  PubMed  Google Scholar 

  • Hall KS, White KO, Rickert VI, Reame N, Westhoff C (2012) Influence of depressed mood and psychological stress symptoms on perceived oral contraceptive side effects and discontinuation in young minority women. Contraception 86:518–525

    Article  PubMed Central  PubMed  Google Scholar 

  • Henderson JA, Shively CA (2004) Triphasic oral contraceptive treatment alters the behavior and neurobiology of female cynomolgus monkeys. Psychoneuroendocrinology 29:21–34

    Article  CAS  PubMed  Google Scholar 

  • Henderson LP (2007) Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: effects on reproductive function. Neuropharmacology 52:1439–1453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ho HP, Olsson M, Westberg L, Melke J, Eriksson E (2001) The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model of premenstrual irritability? Neuropsychopharmacology 24:502–510

    Article  CAS  PubMed  Google Scholar 

  • Johansson IM, Birzniece V, Lindblad C, Olsson T, Backstrom T (2002) Allopregnanolone inhibits learning in the Morris water maze. Brain Res 934:125–131

    CAS  PubMed  Google Scholar 

  • Kask K, Backstrom T, Nilsson LG, Sundstrom-Poromaa I (2008) Allopregnanolone impairs episodic memory in healthy women. Psychopharmacology (Berl) 199:161–168

    Article  CAS  Google Scholar 

  • Khisti RT, Chopde CT, Jain SP (2000) Antidepressant-like effect of the neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice forced swim test. Pharmacol Biochem Behav 67:137–143

    Google Scholar 

  • Kulkarni J (2007) Depression as a side effect of the contraceptive pill. Expert Opin Drug Saf 6:371–374

    Article  CAS  PubMed  Google Scholar 

  • Kurshan N, Epperson CN (2006) Oral contraceptives and mood in women with and without premenstrual dysphoria: a theoretical model. Arch Womens Ment Health 9:1–14

    Article  CAS  PubMed  Google Scholar 

  • Lobo RA, Stanczyk FZ (1994) New knowledge in the physiology of hormonal contraceptives. Am J Obstet Gynecol 170:1499–1507

    Article  CAS  PubMed  Google Scholar 

  • Loose-Mitchell DS, Stancel GM (2001) Estrogens and progestins. In: Hardman JG, Limbird LE, Goodman Gilman A (eds) Goodman & Gilman's the pharmacological basis of therapeutics, 10th edn. McGraw Hill, New York, p 1597

    Google Scholar 

  • Mayo W, Dellu F, Robel P, Cherkaoui J, Le Moal M, Baulieu EE, Simon H (1993) Infusion of neurosteroids into the nucleus basalis magnocellularis affects cognitive processes in the rat. Brain Res 607:324–328

    CAS  PubMed  Google Scholar 

  • Miczek KA, Fish EW, De Bold JF (2003) Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm Behav 44:242–257

    Article  CAS  PubMed  Google Scholar 

  • Nadler RD, Dahl JF, Collins DC, Gould KG (1992) Hormone levels and anogenital swelling of female chimpanzees as a function of estrogen dosage in a combined oral contraceptive. Proc Soc Exp Biol Med 201:73–79

    Article  CAS  PubMed  Google Scholar 

  • Nilsson A, Jacobson L, Ingemanson CA (1967) Side-effects of an oral contraceptive with particular attention to mental symptoms and sexual adaptation. Acta Obst et Gynec Scandinav 46:537–556

    Article  Google Scholar 

  • Oinonen KA, Mazmanian D (2002) To what extent do oral contraceptives influence mood and affect? J Affect Disord 70:229–240

    Article  CAS  PubMed  Google Scholar 

  • Paoletti AM, Lello S, Fratta S, Orru M, Ranuzzi F, Sogliano C, Concas A, Biggio G, Melis GB (2004) Psychological effect of the oral contraceptive formulation containing 3 mg of drospirenone plus 30 μg of ethinyl estradiol. Fertil Steril 81:645–651

    Article  CAS  PubMed  Google Scholar 

  • Pearson Murphy BE, Steinberg SI, Hu FY, Allison CM (2001) Neuroactive ring A-reduced metabolites of progesterone in human plasma during pregnancy: elevated levels of 5α-dihydroprogesterone in depressed patients during the latter half of pregnancy. J Clin Endocrinol Metab 86:5981–5987

    CAS  PubMed  Google Scholar 

  • Pisu MG, Serra M (2004) Neurosteroids and neuroactive drugs in mental disorders. Life Sci 74:3181–3197

    Article  CAS  PubMed  Google Scholar 

  • Porcu P, Mostallino MC, Sogliano C, Santoru F, Berretti R, Concas A (2012) Long-term administration with levonorgestrel decreases allopregnanolone levels and alters GABAA receptor subunit expression and anxiety-like behavior. Pharmacol Biochem Behav 102:366–372

    Article  CAS  PubMed  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    CAS  PubMed  Google Scholar 

  • Prasad A, Imamura M, Prasad C (1997) Dehydroepiandrosterone decreases behavioral despair in high- but not low-anxiety rats. Physiol Behav 62:1053–1057

    Article  CAS  PubMed  Google Scholar 

  • Purdy RH, Morrow AL, Blinn JR, Paul SM (1990) Synthesis, metabolism, and pharmacological activity of 3α-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes. J Med Chem 33:1572–1581

    Article  CAS  PubMed  Google Scholar 

  • Rapkin AJ, Biggio G, Concas A (2006a) Oral contraceptives and neuroactive steroids. Pharmacol Biochem Behav 84:628–634

    Article  CAS  PubMed  Google Scholar 

  • Rapkin AJ, Morgan M, Goldman L, Brann DW, Simone D, Mahesh VB (1997) Progesterone metabolite allopregnanolone in women with premenstrual syndrome. Obstet Gynecol 90:709–714

    Article  CAS  PubMed  Google Scholar 

  • Rapkin AJ, Morgan M, Sogliano C, Biggio G, Concas A (2006b) Decreased neuroactive steroids induced by combined oral contraceptive pills are not associated with mood changes. Fertil Steril 85:1371–1378

    Article  PubMed  Google Scholar 

  • Romeo E, Strohle A, Spalletta G, di Michele F, Hermann B, Holsboer F, Pasini A, Rupprecht R (1998) Effects of antidepressant treatment on neuroactive steroids in major depression. Am J Psychiatry 155:910–913

    Google Scholar 

  • Sanchez Montoya EL, Hernandez L, Barreto-Estrada JL, Ortiz JG, Jorge JC (2010) The testosterone metabolite 3α-diol enhances female rat sexual motivation when infused in the nucleus accumbens shell. J Sex Med 7:3598–3609

    Article  PubMed  Google Scholar 

  • Sanders SA, Graham CA, Bass JL, Bancroft J (2001) A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation. Contraception 64:51–58

    Article  CAS  PubMed  Google Scholar 

  • Sassoè-Pognetto M, Follesa P, Panzanelli P, Perazzini AZ, Porcu P, Sogliano C, Cherchi C, Concas A (2007) Fluctuations in brain concentrations of neurosteroids are not associated to changes in gephyrin levels. Brain Res 1169:1–8

    PubMed  Google Scholar 

  • Segebladh B, Borgstrom A, Odlind V, Bixo M, Sundstrom-Poromaa I (2009) Prevalence of psychiatric disorders and premenstrual dysphoric symptoms in patients with experience of adverse mood during treatment with combined oral contraceptives. Contraception 79:50–55

    Article  CAS  PubMed  Google Scholar 

  • Serra M, Sanna E, Mostallino MC, Biggio G (2007) Social isolation stress and neuroactive steroids. Eur Neuropsychopharmacol 17:1–11

    Article  CAS  PubMed  Google Scholar 

  • Soma KK, Scotti MA, Newman AE, Charlier TD, Demas GE (2008) Novel mechanisms for neuroendocrine regulation of aggression. Front Neuroendocrinol 29:476–489

    Article  CAS  PubMed  Google Scholar 

  • Strufaldi R, Pompei LM, Steiner ML, Cunha EP, Ferreira JA, Peixoto S, Fernandes CE (2010) Effects of two combined hormonal contraceptives with the same composition and different doses on female sexual function and plasma androgen levels. Contraception 82:147–154

    Article  CAS  PubMed  Google Scholar 

  • Stuckey BG (2008) Female sexual function and dysfunction in the reproductive years: the influence of endogenous and exogenous sex hormones. J Sex Med 5:2282–2290

    Article  CAS  PubMed  Google Scholar 

  • Tennent BJ, Smith ER, Davidson JM (1980) The effects of estrogen and progesterone on female rat proceptive behavior. Horm Behav 14:65–75

    Article  CAS  PubMed  Google Scholar 

  • Toffol E, Heikinheimo O, Koponen P, Luoto R, Partonen T (2012) Further evidence for lack of negative associations between hormonal contraception and mental health. Contraception 86:470–480

    Google Scholar 

  • Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A (1998) Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci U S A 95:3239–3244

    Google Scholar 

  • Van de Poll NE, Taminiau MS, Endert E, Louwerse AL (1988) Gonadal steroid influence upon sexual and aggressive behavior of female rats. Int J Neurosci 41:271–286

    PubMed  Google Scholar 

  • Wallwiener M, Wallwiener LM, Seeger H, Mueck AO, Zipfel S, Bitzer J, Wallwiener CW (2010) Effects of sex hormones in oral contraceptives on the female sexual function score: a study in German female medical students. Contraception 82:155–159

    Article  CAS  PubMed  Google Scholar 

  • Wang M (2011) Neurosteroids and GABA-A receptor function. Front Endocrinol (Lausanne) 2:44

    Google Scholar 

  • Wang M, Seippel L, Purdy RH, Backstrom T (1996) Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one. J Clin Endocrinol Metab 81:1076–1082

    CAS  PubMed  Google Scholar 

  • Welling LL (2013) Psychobehavioral effects of hormonal contraceptive use. Evol Psychol 11:718–742

    PubMed  Google Scholar 

  • Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 134:319–329

    Article  CAS  Google Scholar 

  • Wu J, Zhu Y (2008) Effects of estrogen and estrogenic compounds on cognition in ovariectomized rats. Climacteric 11:212–220

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The experiments comply with the current laws of the Italian country. This article is dedicated to the memory of Dr. Robert H Purdy for his pioneering work on neuroactive steroids. We express profound gratitude for his generous scientific expertise and invaluable advice.

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The authors have no conflicts of interest to report.

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Authors and Affiliations

  1. Department of Life and Environment Sciences, University of Cagliari, SS 554 (Km. 4,500), 09042, Monserrato, Cagliari, Italy

    Francesca Santoru, Roberta Berretti, Andrea Locci & Alessandra Concas

  2. Neuroscience Institute, National Research Council of Italy (CNR), Cagliari, Italy

    Patrizia Porcu & Alessandra Concas

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  1. Francesca Santoru
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  2. Roberta Berretti
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  3. Andrea Locci
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  4. Patrizia Porcu
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  5. Alessandra Concas
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Correspondence to Alessandra Concas.

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Santoru, F., Berretti, R., Locci, A. et al. Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats. Psychopharmacology 231, 3351–3364 (2014). https://doi.org/10.1007/s00213-014-3539-9

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