Pathways of sexual desire

Journal of Sexual Medicine

Volumn 6, Issue 6, 2009, Pages 1506-1533

  Pfaus, James G ^a  

^a and Applied Physiology   (Canada)

Author keywords

Hypoactive sexual desire disorder; Libido; Neuropharmacology; Sexual desire; Treatment

Indexed keywords

2 DIPROPYLAMINO 8 HYDROXYTETRALIN; BREMELANOTIDE; CANNABINOID RECEPTOR AGONIST; CANNABINOID RECEPTOR ANTAGONIST; DOPAMINE; DOPAMINE RECEPTOR STIMULATING AGENT; DRONABINOL; ENDOCANNABINOID; ESTRADIOL; ESTRADIOL BENZOATE; FENCLONINE; FLIBANSERIN; FLUOXETINE; LEVODOPA; MELANOCORTIN; MELANOTAN II; NALOXONE; NORADRENALIN; OPIATE; OXYTOCIN; PROGESTERONE; SEROTONIN; SEROTONIN 2 AGONIST; SEROTONIN ANTAGONIST; SEROTONIN UPTAKE INHIBITOR; STEROID HORMONE; TESTOSTERONE; YOHIMBINE;

DOPAMINE RELEASE; DOPAMINERGIC SYSTEM; DRUG MECHANISM; EJACULATION; EROTISM; EVENT RELATED POTENTIAL; EXCITATORY POSTSYNAPTIC POTENTIAL; FEMALE; HORMONE ACTION; HORMONE SUBSTITUTION; HUMAN; HYPOACTIVE SEXUAL DESIRE DISORDER; HYPOTHALAMUS; INCERTOHYPOTHALAMIC DOPAMINERGIC SYSTEM; LIBIDO; LIMBIC SYSTEM; LORDOSIS; MALE; MENOPAUSE; MESOLIMBIC DOPAMINERGIC SYSTEM; NAUSEA; NERVE STIMULATION; NEUROPHYSIOLOGY; NONHUMAN; NORADRENALIN RELEASE; OXYTOCIN RELEASE; PRIORITY JOURNAL; REVIEW; SATIETY; SEDATION; SEROTONIN RELEASE; SEROTONINERGIC SYSTEM; SEXUAL AROUSAL; SEXUAL BEHAVIOR; SEXUAL DESIRE; SEXUAL DYSFUNCTION; SEXUAL EXCITATION; SEXUAL INHIBITION; SEXUAL REWARD; SIDE EFFECT; SYSTOLIC BLOOD PRESSURE; THALAMUS MIDLINE NUCLEUS; VENTRAL TEGMENTUM; VISUAL STIMULATION;

EID: 66749115953     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/j.1743-6109.2009.01309.x     Document Type: Review

References (243)

1. American Psychiatric Association. Diagnostic and statistical manual of psychiatric disorders IV-TR (Text Revision). Washington, DC: APA Press; 2000.
2. Robinson TE, Berridge KC. The neural basis of drug craving: An incentive-sensitization theory of addiction. Brain Res Rev 1993;18:247-91.
3. Basson R, McInnes R, Smith MD, Hodgson G, Koppiker N. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. J Womens Health Gend Based Med 2002;11:367-77.
4. Toledano RR, Pfaus JG. The Sexual Arousal and Desire Inventory (SADI): A multidimensional scale to assess sexual arousal and desire. J Sex Med 2006;3: 853-77.
5. Pfaff DW. Drive: Neurobiological and molecular mechanisms of sexual motivation. Cambridge, MA: MIT Press; 1999.
6. Pfaus JG, Kippin TE, Coria-Avila GA. What can animal models tell us about human sexual response? Annu Rev Sex Res 2003;14:1-63.
7. McCall K, Meston C. Cues resulting in desire for sexual activity in women. J Sex Med 2006;5:838-52.
8. Whalen RE. Sexual motivation. Psychol Rev 1964;73:151-63.
9. Kaplan HS. The new sex therapy, Vol 1. New York: Brunel/Mazel; 1974.
10. Masters WH, Johnson VE. Human sexual response. New York: Bantam Books; 1966.
11. McClintock MK. Group mating in the domestic rat as a context for sexual selection: Consequences for the analysis of sexual behavior and neuroendocrine responses. Adv Stud Behav 1984;14:1-50.
12. Coria-Avila GA, Solomon CE, Vargas EB, Lemme I, Ryan R, Ménard S, Gavrila AM, Pfaus JG. Neurochemical basis of conditioned partner preference in the female rat: I. Disruption by naloxone. Behav Neurosci 2008;122:385-95.
13. Kippin TE, Pfaus JG. The development of olfactory conditioned ejaculatory preferences in the male rat. I. Nature of the unconditioned stimulus. Physiol Behav 2001;73:457-69.
14. de Jong TR, Veening JG, Olivier B, Waldinger MD. Oxytocin involvement in SSRI-induced delayed ejaculation: A review of animal studies. J Sex Med 2007;4: 14-28.
15. de Jong TR, Pattij T, Veening JG, Waldinger MD, Cools AR, Olivier B. Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: Comparison of fluvoxamine and paroxetine. Psychopharmacology (Berl) 2005;179:509-15.
16. Pattij T, Olivier B, Waldinger MD. Animal models of ejaculatory behavior. Curr Pharm Des 2005;11:4069-77.
17. Pfaus JG. Revisiting the concept of sexual motivation. Annu Rev Sex Res 1999;10:120-57.
18. Erskine MS. Solicitation behavior in the estrous female rat: A review. Horm Behav 1989;23:473-502.
19. Beach FA. Sexual attractivity, proceptivity, and receptivity in female mammals. Horm Behav 1976;7:105-38.
20. Pfaus JG, Giuliano F, Gelez H. Bremelanotide: An overview of preclinical CNS effects on female sexual function. J Sex Med 2007;4(4 suppl):269-79.
21. Ågmo A, Berenfeld R. Reinforcing properties of ejaculation in the male rat: The role of opioids and dopamine. Behav Neurosci 1990;104:177-82.
22. Coria-Avila GA, Ouimet AJ, Pacheco P, Manzo J, Pfaus JG. Olfactory conditioned partner preference in the female rat. Behav Neurosci 2005;119:716-25.
23. Kippin TE, Sotiropoulos V, Badih J, Pfaus JG. Opposing roles of the nucleus accumbens and anterior lateral hypothalamic area in the control of sexual behaviour in the male rat. Eur J Neurosci 2004;19:698-704.
24. Paredes RG, Martínez I. Naloxone blocks place preference conditioning after paced mating in female rats. Behav Neurosci 2001;115:1363-7.
25. Paredes RG, Vazquez B. What do female rats like about sex? Paced mating. Behav Brain Res 1999;105:117-27.
26. Mehrara BJ, Baum MJ. Naloxone disrupts the expression but not the acquisition by male rats of a conditioned place preference response for an oestrous female. Psychopharamacology (Berl) 1990;101:118-25.
27. Gray JA. The neuropsychology of anxiety. Oxford: Oxford University Press; 1987.
28. Bancroft J, Jannsen E. The dual control model of male sexual response: A theoretical approach to centrally mediated erectile dysfunction. Neurosci Biobehav Rev 2000;24: 571-9.
29. Perelman MA. A new combination treatment for premature ejaculation: A sex therapist's perspective. J Sex Med 2006;3:1004-12.
30. Abel EL. A review of alcohol's effects on sex and reproduction. Drug Alcohol Depend 1980;5:321-32.
31. Castilla J, Barrio G, Belza M, de la Fuente L. Drug and alcohol consumption and sexual risk behavior among young adults: Results from a national survey. Drug Alcohol Depend 1999;56:47-53.
32. Bancroft J, Janssen E, Strong D, Carnes L, Vukadinovic Z, Long LS. The relation between mood and sexuality in heterosexual men. Arch Sex Behav 2003;32:217-30.
33. Kow LM, Pfaff DW. Transmitter and peptide actions on hypothalamic neurons in vitro: Implications for lordosis. Brain Res Bull 1988;20:857-61.
34. Parsons B, Rainbow TC, Pfaff DW, McEwen BS. Hypothalamic protein synthesis essential for the activation of the lordosis reflex in the female rat. Endocrinology 1982;110:620-4.
35. Pfaff DW. Estrogens and brain function. New York: Springer; 1980.
36. Everitt BJ. Sexual motivation: A neural and behavioural analysis of the mechanisms underlying appetitive and copulatory responses of male rats. Neurosci Biobehav Rev 1990;14:217-32.
37. Kingsberg SA. The impact of aging on sexual function in women and their partners. Arch Sex Behav 2002;31:431-7.
38. Pfaus JG, Smith WJ, Coopersmith CB. Appetitive and consummatory sexual behaviors of female rats in bilevel chambers. I. A correlational and factor analysis and the effects of ovarian hormones. Horm Behav 1999;35:224-40.
39. RedoutéJ, Stoléru S, Pugeat M, Costes N, Lavenne F, Le Bars D, Dechaud H, Cinotti L, Pujol JF. Brain processing of visual sexual stimuli in treated and untreated hypogonadal patients. Psychoneuroendocrinology 2005;30:461-82.
40. Sakuma Y. Neural substrates for sexual preference and motivation in the female and male rat. Ann N Y Acad Sci 2008;1129:55-60.
41. McCall K, Meston C. Differences between pre- and postmenopausal women in cues for sexual desire. J Sex Med 2007;4:364-71.
42. Wylie K, Daines B, Jannini EA, Hallam-Jones R, Boul L, Wilson L, Athanasiadis L, Brewster M, Kristensen E. Loss of sexual desire in the postmenopausal woman. J Sex Med 2007;4:395-405.
43. Corona G, Petrone L, Mannucci E, Ricca V, Balercia G, Giommi R, Forti G, Maggi M. The impotent couple: Low desire. Int J Androl 2005;28(2 suppl):46-52.
44. Christensen LW, Clemens LG. Intrahypothalamic implants of testosterone or estradiol and resumption of masculine sexual behavior in long-term castrated male rats. Endocrinology 1974;95:984-90.
45. Södersten P, Larsson K. Sexual behavior in castrated male rats treated with monoamine synthesis inhibitors and testosterone. Pharmacol Biochem Behav 1976;5: 319-27.
46. Smith ER, Damassa DA, Davidson JM. Plasma testosterone and sexual behavior following intracerebral implantation of testosterone propionate in the castrated male rat. Horm Behav 1977;8:77-87.
47. Beach FA, Jordan L. Sexual exhaustion and recovery in the male rat. Q J Exp Psychol 1956;8:121-33.
48. Larsson K. Conditioning and sexual behavior in the male albino rat. Acta Physiol Gothoburgensia 1956;1:1-269.
49. Fernandez-Guasti A, Swaab D, Rodríguez-Manzo G. Sexual behavior reduces hypothalamic androgen receptor immunoreactivity. Psychoneuroendocrinology 2003;28: 501-12.
50. Bolling JL, Blandau RJ. The estrogen-progesterone induction of mating responses in the spayed female rat. Endocrinology 1939;25:359-64.
51. Jones SL, Pfaus JG. Sexual behavior in ovariectomized Wistar rats following varied doses of testosterone with or without estrogen, and the effects of repeated exposure to testosterone. Meeting of the Canadian Association for Neuroscience, Montréal, QC. 2008.
52. Stanislaw H, Rice FJ. Correlation between sexual desire and menstrual cycle characteristics. Arch Sex Behav 1988;17:499-508.
53. Stuckey BG. Female sexual function and dysfunction in the reproductive years: The influence of endogenous and exogenous sex hormones. J Sex Med 2008;5:2282-90.
54. Tarín JJ, Gómez-Piquer V. Do women have a hidden heat period? Hum Reprod 2002;17:2243-8.
55. Wallen K, Winston LA, Gaventa S, Davis-DaSilva M, Collins DC. Periovulatory changes in female sexual behaviour and patterns of ovarian steroid secretion in group-living rhesus monkeys. Horm Behav 1984;18:431-50.
56. Hampson E. Variations in sex-related cognitive abilities across the menstrual cycle. Brain Cogn 1990;14:26-43.
57. McCormick CM, Teillon SM. Menstrual cycle variation in spatial ability: Relation to salivary cortisol levels. Horm Behav 2001;39:29-38.
58. Mordecai KL, Rubin LH, Maki PM. Effects of menstrual cycle phase and oral contraceptive use on verbal memory. Horm Behav 2008;54:286-93.
59. Sherwin BB. Estrogen and cognitive functioning in women. Endocr Rev 2003;24:133-51.
60. Slob AK, Bax CM, Hop WC, Rowland DL, van der Werff ten Bosch JJ. Sexual arousability and the menstrual cycle. Psychoneuroendocrinology 1996;21:545-58.
61. Krug R, Plihal W, Fehm HL, Born J. Selective influence of the menstrual cycle on perception of stimuli with reproductive significance: An event-related potential study. Psychophysiology 2000;37:111-22.
62. Gizewski ER, Krause E, Karama S, Baars A, Senf W, Forsting M. There are differences in cerebral activation between females in distinct menstrual phases during viewing of erotic stimuli: A fMRI study. Exp Brain Res 2006;174:101-8.
63. Archer JS, Love-Geffen TE, Herbst-Damm KL, Swinney DA, Chang JR. Effect of estradiol versus estradiol and testosterone on brain-activation patterns in postmenopausal women. Menopause 2006;13: 528-37.
64. Sherwin BB, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: A prospective, crossover study of sex steroid administration in surgical menopause. Psychosom Med 1985;47:339-51.
65. Kingsberg SA. Testosterone treatment for hypoactive sexual desire disorder in postmenopausal women. J Sex Med 2007;4 (3 suppl):227-34.
66. Segraves RT. Management of hypoactive sexual desire disorder. Adv Psychosom Med 2008;29:23-32.
67. Hull EM, Lorrain DS, Du J, Matuszewich L, Lumley LA, Putnam SK, Moses J. Hormone-neurotransmitter interactions in the control of sexual behavior. Behav Brain Res 1999;105:105-16.
68. Roth RH, Elsworth JD. Biochemical pharmacology of midbrain dopamine neurons. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The fourth generation of progress. New York: Raven; 1995:227-44.
69. Moore KE, Looklingland KJ. Dopaminergic neuronal systems in the hypothalamus. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The fourth generation of progress. New York: Raven; 1995:245-56.
70. Blackburn JR, Pfaus JG, Phillips AG. Dopamine functions in appetitive and defensive behaviours. Prog Neurobiol 1992;39:247-79.
71. Hoshina Y, Takeo T, Nakano K, Sato T, Sakuma Y. Axon-sparing lesion of the preoptic area enhances receptivity and diminishes proceptivity among components of female rat sexual behavior. Behav Brain Res 1994;61:197-204.
72. Paredes RG, Baum MJ. Role of the medial preoptic area/anterior hypothalamus in the control of masculine sexual behavior. Annu Rev Sex Res 1997;8:68-101.
73. Liu YC, Sachs BD, Salamone JD. Sexual behavior in male rats after radiofrequency or dopamine-depleting lesions in nucleus accumbens. Pharmacol Biochem Behav 1998;60:585-92.
74. Guarraci FA, Megroz AB, Clark AS. Effects of ibotenic acid lesions of the nucleus accumbens on paced mating behavior in the female rat. Behav Neurosci 2002;116:568-76.
75. Hull EM, Warner RK, Bazzett TJ, Eaton RC, Thompson JT, Scaletta LL. D2/ D1 ratio in the medial preoptic area affects copulation of male rats. J Pharmacol Exp Ther 1989;251:422-7.
76. HyyppäM, Rinne UK, Sonninen V. The activating effect of L-dopa treatment on sexual functions and its experimental background. Acta Neurol Scand 1970;46(43 suppl):223-6.
77. Malmnäs CO. Dopaminergic reversal of the decline after castration of rat copulatory behaviour. J Endocrinol 1977;73:187-8.
78. Malmnäs CO. The significance of dopamine, versus other catecholamines, for L-dopa induced facilitation of sexual behavior in the castrated male rat. Pharmacol Biochem Behav 1976;4:521-6.
79. Heaton JP, Varrin SJ, Morales A. The characterization of a bio-assay of erectile function in a rat model. J Urol 1991;145:1099-102.
80. Lal S, Ackman D, Thavundayil JX, Kiely ME, Etienne P. Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects. Prog Neuropsychopharmacol Biol Psychiatry 1984;8:695-9.
81. Foreman MM, Hall JL. Effects of D2-dopaminergic receptor stimulation on male rat sexual behavior. J Neural Transm 1987;68:153-70.
82. McIntosh TK, Barfield RJ. Brain monoaminergic control of male reproductive behavior. II. Dopamine and the post-ejaculatory refractory period. Behav Brain Res 1984;12:267-73.
83. Pfaus JG, Phillips AG. Role of dopamine in anticipatory and consummatory aspects of sexual behavior in the male rat. Behav Neurosci 1991;105:727-43.
84. Pfaus JG, Phillips AG. Differential effects of dopamine receptor antagonists on the sexual behavior of male rats. Psychopharmacology (Berl) 1989;98: 363-8.
85. Grierson JP, James MD, Pearson JR, Wilson CA. The effect of selective D1 and D2 dopaminergic agents on sexual receptivity in the female rat. Neuropharmacology 1988;27:181-9.
86. Becker JB. Direct effect of 17 beta-estradiol on striatum: Sex differences in dopamine release. Synapse 1990;5:157-64.
87. Sanderson NS, Le B, Zhou Z, Crews D. Preoptic neuronal nitric oxide synthase induction by testosterone is consistent with a role in gating male copulatory behavior. Eur J Neurosci 2008;27:183-90.
88. Sato S, Braham CS, Putnam SK, Hull EM. Neuronal nitric oxide synthase and gonadal steroid interaction in the MPOA of male rats: Co-localization and testosterone-induced restoration of copulation and nNOS-immunoreactivity. Brain Res 2005;1043:205-13.
89. Pfaus JG, Kippin TE, Centeno S. Conditioning and sexual behavior: A review. Horm Behav 2001;40:291-321.
90. Meisel RD, Sachs BD. The physiology of male reproducation. In: Knobil E, Neil JD, eds. The physiology of reproduction, Vol. 2. New York: Raven Press; 1994:3-105.
91. Fiorino DF, Coury A, Phillips AG. Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect in male rats. J Neurosci 1997;17:4849-55.
92. Moore RY, Bloom FE. Central catecholamine neuron systems: Anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci 1979;2:113-68.
93. Green JD, Clemente CD, de Groot J. Rhinencephalic lesions and behavior in cats: An analysis of the Kluver-Bucy syndrome with particular reference to normal and abnormal sexual behavior. J Comp Neurol 1957;108:505-45.
94. Cooper JR, Bloom FE, Roth RH. The biochemical basis of neuropharmacology. 6th edition. New York: Oxford University Press; 1991.
95. Ramírez OA, Carrer HF. Effect of estrogen and progesterone priming on the uptake and release of serotonin and noradrenaline from the ventromedial hypothalamus. Acta Physiol Lat Am 1982;32:313-9.
96. Fernández-Guasti A, Larsson K, Beyer C. Potentiative action of alpha- and beta-adrenergic receptor stimulation in inducing lordosis behavior. Pharmacol Biochem Behav 1985;22:613-7.
97. Weiland NG, Wise PM. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions. Endocrinology 1987;121:1751-8.
98. Etgen AM. Intrahypothalamic implants of noradrenergic antagonists disrupt lordosis behavior in female rats. Physiol Behav 1990;48:31-46.
99. Malmnäs CO. Monoaminergic influence on testosterone-activated copulatory behavior in the castrated male rat. Acta Physiol Scand 1973;395:1-128.
100. Clark JT, Smith ER. Clonidine suppresses copulatory behavior and erectile reflexes in male rats: Lack of effect of naloxone pretreatment. Neuroendocrinology 1990;51:357-64.
101. Meston CM, Gorzalka BB, Wright JM. Inhibition of physiological and subjective sexual arousal in women by clonidine. Psychosom Med 1997;59:399-407.
102. Allard J, Giuliano F. Central nervous system agents in the treatment of erectile dysfunction: How do they work? Curr Urol Rep 2001;2:488-94.
103. Rodríguez-Manzo G, Fernández-Guasti A. Reversal of sexual exhaustion by serotonergic and noradrenergic agents. Behav Brain Res 1994;62:127-34.
104. Clark JT. Sexual arousal and performance are modified by adrenergic-neuropeptide-steroid interactions. In: Bancroft J, ed. The pharmacology of sexual function and dysfunction. Amsterdam: Excerpta Medica; 1995:55-68.
105. McIntosh TK, Barfield RJ. Brain monoaminergic control of male reproductive behavior. III. Norepinephrine and the post-ejaculatory refractory period. Behav Brain Res 1984b;12:275-81.
106. Voisey J, Carroll L, van Daal A. Melanocortins and their receptors and antagonists. Curr Drug Targets 2003;4:586-97.
107. Oosterom J, Nijenhuis WA, Schaaper WM, Slootstra J, Meloen RH, Gispen WH, Burbach JP, Adan RA. Conformation of the core sequence in melanocortin peptides directs selectivity for the melanocortin MC3 and MC4 receptors. J Biol Chem 1999;274: 16853-60.
108. Heisler LK, Cowley MA, Kishi T, Tecott LH, Fan W, Low MJ, Smart JL, Rubinstein M, Tatro JB, Zigman JM, Cone RD, Elmquist JK. Central serotonin and melanocortin pathways regulating energy homeostasis. Ann N Y Acad Sci 2003;994:169-74.
109. O'Donohue T, Dorsa D. The opiomelanotropinergic neuronal and endocrine system. Peptides 1982;3:353-95.
110. Medina F, Siddiqui A, Scimonelli T, Fenske C, Wilson CA, Celis ME. The inter-relationship between gonadal steroids and POMC peptides, beta-endorphin and alpha-MSH, in the control of sexual behavior in the female rat. Peptides 1998;19:1309-16.
111. Wilson CA, Thody AJ, Hole DR, Grierson JP, Celis ME. Interaction of estradiol, alpha-melanocyte-stimulating hormone, and dopamine in the regulation of sexual receptivity in the female rat. Neuroendocrinology 1991;54:14-22.
112. Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties, and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res 2004;16:51-9.
113. Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. Evaluation of the safety, pharmadokinetics, and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Int J Impot Res 2004;16:135-42.
114. Hadley ME. Discovery that a melanocortin regulates sexual functions in male and female humans. Peptides 2005;26:1687-9.
115. Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R. An effect of the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex Med 2006;3:628-38.
116. Pfaus JG, Shadiack A, Van Soest T, Tse M, Molinoff P. Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proc Natl Acad Sci U S A 2004;101:10201-4.
117. Rössler AS, Pfaus JG, Kia HK, BernabéJ, Alexandre L, Giuliano F. The melanocortin agonist, melanotanII, enhances proceptive sexual behaviors in the female rat. Pharmacol Biochem Behav 2006;85:514-21.
118. Carter CS, Williams JR, Witt DM, Insel TR. Oxytocin and social bonding. Ann N Y Acad Sci 1992;652:204-11.
119. Young LJ, Wang Z. The neurobiology of pair bonding. Nat Neurosci 2004;7:1048-54.
120. Caldwell JD, Jirikowski GF, Greer ER, Pedersen CA. Medial preoptic area oxytocin and female sexual receptivity. Behav Neurosci 1989;103:655-62.
121. Schulze HG, Gorzalka BB. Oxytocin effects on lordosis frequency and lordosis duration following infusion into the medial pre-optic area and ventromedial hypothalamus of female rats. Neuropeptides 1991;18:99-106.
122. Kita I, Yoshida Y, Nishino S. An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection. Neurosci Res 2006;54: 269-75.
123. Cantor JM, Binik YM, Pfaus JG. Chronic fluoxetine inhibits sexual behavior in the male rat: Reversal with oxytocin. Psychopharmacology (Berl) 1999;144:355-62.
124. Hillegaart V, Alster P, Uvnäs-Moberg K, Ahlenius S. Sexual motivation promotes oxytocin secretion in male rats. Peptides 1998;19:39-45.
125. Ménard S, Coria-Avila GA, Gélèz H, Godfrey J, Sorochinski M, Pfaus JG. Activation of oxytocin and vasopressin neurons following the presentation of an odour associated with sexual reward in the male rat. Ninth Annual Meeting of the Society for Behavioral Neuroendocrinology, Austin, TX.
126. Succu S, Sanna F, Melis T, Boi A, Argiolas A, Melis MR. Stimulation of dopamine receptors in the paraventricular nucleus of the hypothalamus of male rats induces penile erection and increases extra-cellular dopamine in the nucleus accumbens: Involvement of central oxytocin. Neuropharmacology 2007;52:1034-43.
127. Saphier D, Feldman S. Electrophysiology of limbic forebrain and paraventricular nucleus connections. Brain Res Bull 1986;17:743-50.
128. Kinsey AC, Pomeroy WB, Martin CE. Sexual behavior in the human male. Philadelphia, PA: W.B. Saunders; 1948.
129. Anastasopoulos G. Hypersexuality, change of character, sleep disorders & acute dementia in a tumor of the right temporal lobe. Psychiatr Neurol (Basel) 1958;136:85-108.
130. Chow TW, Cummings JL. Neuropsychiatry: Clinical assessment and approach to diagnosis. In: Sadock BJ, Sadock VA, eds. Comprehensive texbook of psychiatry. 7th edition. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:221-41.
131. Góscínski I, Kwiatkowski S, Polak J, Orlowiejska M, Partyk A. The Kluver-Bucy syndrome. J Neurosurg Sci 1997;41:269-72.
132. Kanowski S. Hypersexuality in relation to partial Klüver-Bucy syndrome (author's transl). J Neurovisc Relat 1971;10:504-16.
133. Robbins TW. Shifting and stopping: Fronto-striatal substrates, neurochemical modulation, and clinical implications. Philos Trans R Soc Lond B Biol Sci 2007;362:917-32.
134. Robbins TW. Dissociating executive functions of the prefrontal cortex. Philos Trans R Soc Lond B Biol Sci 1996;351:1463-70.
135. Andrés P. Supervisory attentional system in patients with focal frontal lesions. Clin J Exp Neuropsychol 2001;23:225-39.
136. Tamm L, Menon V, Reiss AL. Maturation of brain function associated with response inhibition. J Am Acad Child Adolesc Psychiatry 2002;41:1231-8.
137. Winn P. Frontal syndrome as a consequence of lesions in the pedunculopontine tegmental nucleus: A short theoretical review. Brain Res Bull 1998;47:551-63.
138. Pfaus JG, Pinel JPJ. Alcohol inhibits and disinhibits sexual behavior in the male rat. Psychobiology 1989;17:195-201.
139. Ferster CB, Skinner BF. Schedules of reinforcement. New York: Appleton-Century-Crofts; 1957.
140. Perper T. Sex signals: The biology of love. Philadelphia, PA: ISI Press; 1985.
141. Toates F. Motivational systems. Cambridge: Cambridge University Press; 1992.
142. Pfaus JG, Gorzalka BB. Opioids and sexual behavior. Neurosci Biobehav Rev 1987;11:1-34.
143. Chessick RD. The "pharmacogenic orgasm"in the drug addict. Arch Gen Psychiat 1960;3:545-56.
144. Whipple B, Komisaruk BR. Elevation of pain threshold by vaginal stimulation in women. Pain 1985;21:357-67.
145. Szechtman H, Hershkowitz M, Simantov R. Sexual behavior decreases pain sensitivity and stimulated endogenous opioids in male rats. Eur J Pharmacol 1981;70: 279-85.
146. Rodríguez-Manzo G, Fernández-Guasti A. Opioid antagonists and the sexual satiation phenomenon. Psychopharmacology (Berl) 1995;122:131-6.
147. Ismail N, Zhao Y, Pfaus JG. Context-dependent acquisition of copulatory behavior in the male rat: Role of female availability. Behav Neurosci 2008;122:991-7.
148. Patterson S, Robson L, Kosterlitz H. Classification of opioid receptors. Br Med Bull 1983;39:31-6.
149. Band LC, Hull EM. Morphine and dynorphin(1-13) microinjected into the medial preoptic area and nucleus accumbens: Effects on sexual behavior in male rats. Brain Res 1990;524:77-84.
150. Hughes AM, Everitt BJ, Herbert J. Selective effects of beta-endorphin infused into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the sexual and ingestive behaviour of male rats. Neuroscience 1987;23:1063-73.
151. Matuszewich L, Ormsby JL, Moses J, Lorrain DS, Hull EM. Effects of morphiceptin in the medial preoptic area on male sexual behavior. Psychopharmacology (Berl) 1995;122: 330-5.
152. Acosta-Martinez M, Etgen AM. Activation of mu-opioid receptors inhibits lordosis behavior in estrogen and progesterone-primed female rats. Horm Behav 2002;41:88-100.
153. Coolen LM, Fitzgerald ME, Yu L, Lehman MN. Activation of mu opioid receptors in the medial preoptic area following copulation in male rats. Neuroscience 2004;124:11-21.
154. Ågmo A, Gómez M. Sexual reinforcement is blocked by infusion of naloxone into the medial preoptic area. Behav Neurosci 1993;107:812-8.
155. Rodríguez-Manzo G, Asai M, Fernández-Guasti A. Evidence for changes in brain enkephalin contents associated to male rat sexual activity. Behav Brain Res 2002;131:47-55.
156. Mitchell JB, Stewart J. Facilitation of sexual behaviors in the male rat associated with intra-VTA injections of opiates. Pharmacol Biochem Behav 1990;35:643-50.
157. Mitchell JB, Gratton A. Mesolimbic dopamine release elicited by activation of the accessory olfactory system: A high-speed chronoamperometric study. Neurosci Lett 1992;140:81-4.
158. van Furth WR, van Ree JM. Sexual motivation: Involvement of endogenous opioids in the ventral tegmental area. Brain Res 1996;729:20-8.
159. Kalivas PW, Abhold R. Enkephalin release into the ventral tegmental area in response to stress: Modulation of mesocorticolimbic dopamine. Brain Res 1987;414:339-44.
160. Yoshida M, Yokoo H, Tanaka T, Mizoguchi K, Emoto H, Ishii H, Tanaka M. Facilitatory modulation of mesolimbic dopamine neuronal activity by a mu-opioid agonist and nicotine as examined with in vivo microdialysis. Brain Res 1993;624:277-80.
161. Bergevin A, Girardot D, Bourque MJ, Trudeau LE. Presynaptic mu-opioid receptors regulate a late step of the secretory process in rat ventral tegmental area GABAergic neurons. Neuropharmacology 2002;42:1065-78.
162. Acosta-Martinez M, Etgen AM. The role of delta-opioid receptors in estrogen facilitation of lordosis behavior. Behav Brain Res 2002;136:93-102.
163. Pfaus JG, Pfaff DW. Mu-, delta-, and kappa-opioid receptor agonists selectively modulate sexual behaviors in the female rat: Differential dependence on progesterone. Horm Behav 1992;26:457-73.
164. Sinchak K, Mills RH, Eckersell CB, Micevych PE. Medial preoptic area delta-opioid receptors inhibit lordosis. Behav Brain Res 2004;155:301-6.
165. McCarthy MM, Malik KF, Feder HH. Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area. Brain Res 1990;507:40-4.
166. Devidze N, Zhang Q, Zhou J, Lee AW, Pataky S, Kow LM, Pfaff DW. Presynaptic actions of opioid receptor agonists in ventromedial hypothalamic neurons in estrogen- and oil-treated female mice. Neuroscience 2008;152:942-9.
167. Lauber AH, Romano GJ, Mobbs CV, Howells RD, Pfaff DW. Estradiol induction of proenkephalin messenger RNA in hypothalamus: Dose-response and relation to reproductive behavior in the female rat. Brain Res Mol Brain Res 1990;8:47-54.
168. Sinchak K, Micevych PE. Progesterone blockade of estrogen activation of mu-opioid receptors regulates reproductive behavior. J Neurosci 2001;21:5723-9.
169. Rodríguez-Manzo G, López-Rubalcava C, Fernández-Guasti A. Anxiolytic-like effect of ejaculation under various sexual behavior conditions in the male rat. Physiol Behav 1999;67:651-7.
170. Pazos MR, Núñez E, Benito C, Tolón RM, Romero J. Functional neuroanatomy of the endocannabinoid system. Pharmacol Biochem Behav 2005;81:239-47.
171. Pars HG, Howes JF. Potential therapeutic agents derived from the cannabinoid nucleus. Adv Drug Res 1977;11:97-189.
172. Mani SK, Mitchell A, O'Malley BW. Progesterone recepetor and dopamine receptors are required in Delta-9-tetrahydrocannabinol modulation of sexual receptivity in female rats. Proc Natl Acad Sci USA 2001;98:1248-54.
173. Baker D, Pryce G, Giovannoni G, Thompson AJ. The therapeutic potential of cannabis. Lancet Neurol 2003;2:291-8.
174. Crenshaw TL, Goldberg JP. Sexual pharmacology: Drugs that affect sexual function. New York: Norton; 1996.
175. Martinez-Gonzalez D, Bonilla-Jaime H, Morales-Otal A, Henriksen SJ, Velazquez-Moctezuma J, Prospero-Garcia O. Oleamide and anandamide effects on food intake and sexual behavior of rats. Neurosci Lett 2004;364:1-6.
176. Navarro M, Fernandez-Ruiz JJ, de Miguel R, Hernandez ML, Cebeira M, Ramos JA. An acute dose of delta 9-tetrahydrocannabinol affects behavioral and neurochemical indices of mesolimbic dopaminergic activity. Behav Brain Res 1993;57:37-47.
177. Gorzalka BB, Morish AD, Hill MN. Endocannabinoid modulation of male sexual behavior. Psychopharmacology (Berl) 2008;198:479-86.
178. Mellis MR, Succu S, Mascia MS, Argiolas A. Antagonism of CB 1 receptors in the paraventricular nucleus of male rats induces penile erection. Neurosci Lett 2004;359:17-20.
179. Succu S, Mascia MS, Sanna F, Melis T, Argiolas A, Melis MR. The cannabinoid CB 1 receptor antagonist SR 141716A induces penile erection by increasing extra-cellular glutamic acid in the paraventricular nucleus of male rats. Behav Brain Res 2006;169:274-81.
180. Turley WA Jr, Floody OR. Delta-9-Tetrahydrocannabinol stimulates receptive and proceptive sexual behaviors in female hamsters. Horm Behav 1980;14:65-75.
181. Ferrari F, Ottani A, Giuliani D. Inhibitory effects of the cannabinoid agonist HU 210 on rat sexual behavior. Physiol Behav 2000;69:547-54.
182. López HH, Webb SA, Nash S. Cannabinoid receptor antagonism increases female sexual motivation. Pharmacol Biochem Behav 2009;92:17-24.
183. Bradshaw HB, Rimmerman N, Krey JF, Walker JM. Sex and hormonal cycle differences in rat brain levels of pain-related cannabimimetic lipid mediators. Am J Physiol Regul Integr Comp Physiol 2006;291:349-58.
184. Gonzalez S, Bisogno T, Wenger T, Manzanares J, Milone A, Berrendero F, Di Marzo V, Ramos JA, Fernandez-Ruiz JJ. Sex steroid influence on cannabinoid CB(1) receptor mRNA and endocannabinoid levels in the anterior pituitary gland. Biochem Biophys Res Commun 2000;270:260-6.
185. Blundell JE. Serotonin manipulations and the structure of feeding behaviour. Appetite 1986;7:39-56.
186. Meyerson BJ. The effect of neuropharmacological agents on hormone-activated estrus behaviour in ovariectomised rats. Arch Int Pharmacodyn Ther 1964;150:4-33.
187. DallóJ. Effect of two brain serotonin depletors on the sexual behavior of male rats. Pol J Pharmacol Pharm 1977;29:247-51.
188. McIntosh TK, Barfield RJ. Brain monoaminergic control of male reproductive behavior. I. Serotonin and the post-ejaculatory refractory period. Behav Brain Res 1984;12:255-65.
189. Marson L, McKenna KE. Serotonergic neurotoxic lesions facilitate male sexual reflexes. Pharmacol Biochem Behav 1994;47:883-8.
190. Vega Matuszcyk J, Larsson K, Eriksson E. The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. Pharmacol Biochem Behav 1998;60:527-32.
191. Mendelson SD. A review and reevaluation of the role of serotonin in the modulation of lordosis behavior in the female rat. Neurosci Biobehav Rev 1992;16:309-50.
192. Bradshaw WG, Erskine MS, Baum MJ. Dissociation of the effects of gonadal steroids on brain serotonin metabolism and sexual behavior in the male rat. Neuroendocrinology 1982;34:38-45.
193. Hoyer D, Martin GR. Classification and nomenclature of 5-HT receptors: A comment on current issues. Behav Brain Res 1996;73:263-8.
194. Ågmo A, Fernández H, Picker Z. Naloxone inhibits the facilitatory effects of 8-OH-DPAT on male rat sexual behaviour. Eur J Pharmacol 1989;166:115-6.
195. Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, Wikström H, Sanchez D, Arvidsson LE, Hacksell U, Nilsson JL. Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav 1981;15:785-92.
196. Schnur SL, Smith ER, Lee RL, Mas M, Davidson JM. A component analysis of the effects of DPAT on male rat sexual behavior. Physiol Behav 1989;45:897-901.
197. Camacho FJ, Castro M, Hernández V, Paredes RG. Facilitation of ejaculation induced by 8-OH-DPAT does not produce conditioned place preference in male rats. Behav Neurosci 2007;121:579-85.
198. Fernández-Guasti A, Rodríguez-Manzo G. Pharmacological and physiological aspects of sexual exhaustion in male rats. Scand J Psychol 2003;44:257-63.
199. Fernández-Guasti A, Rodríguez-Manzo G. 8-OH-DPAT and male rat sexual behavior: Partial blockade by noradrenergic lesion and sexual exhaustion. Pharmacol Biochem Behav 1997;56:111-6.
200. Klint T, Dahlgren IL, Larsson K. The selective 5-HT2 receptor antagonist amperozide attenuates 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced inhibition of male rat sexual behavior. Eur J Pharmacol 1992;212:241-6.
201. Watson NV, Gorzalka BB. DOI-induced inhibition of copulatory behavior in male rats: Reversal by 5-HT2 antagonists. Pharmacol Biochem Behav 1991;39:605-12.
202. Paredes RG, Contreras JL, Agmo A. Serotonin and sexual behavior in the male rabbit. J Neural Transm 2000;107:767-77.
203. Yells DP, Prendergast MA, Hendricks SE, Nakamura M. Fluoxetine-induced inhibition of male rat copulatory behavior: Modification by lesions of the nucleus paragigantocellularis. Pharmacol Biochem Behav 1994;49:121-7.
204. Beitz AJ. The nuclei of origin of brainstem serotonergic projections to the rodent spinal trigeminal nucleus. Neurosci Lett 1982;32:223-8.
205. Fernández-Guasti A, Escaalante AL, Ahlenius S, Hillegaart V, Larsson K. Stimulation of 5-HT1A and 5-HT1B receptors in brain regions and its effects on male rat sexual behaviour. Eur J Pharmacol 1992;210:121-9.
206. Lorrain DS, Matuszewich L, Hull EM. 8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial preoptic area of male rats. Brain Res 1998;790:217-23.
207. Damsma G, Pfaus JG, Wenkstern D, Phillips AG, Fibiger HC. Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: Comparison with novelty and locomotion. Behav Neurosci 1992;106:181-91.
208. Lorrain DS, Matuszewich L, Friedman RD, Hull EM. Extracellular serotonin in the lateral hypothalamic area is increased during the postejaculatory interval and impairs copulation in male rats. J Neurosci 1997;17:9361-6.
209. Lorrain DS, Riolo JV, Matuszewich L, Hull EM. Lateral hypothalamic serotonin inhibits nucleus accumbens dopamine: Implications for sexual satiety. J Neurosci 1999;19:7648-52.
210. Sarkar J, Hiegel C, Ginis GE, Hilburn E, Uphouse L. Subchronic treatment with fluoxetine attenuates the effects of acute fluoxetine on female rats' sexual behavior. Brain Res 2008;1190:56-64.
211. Matuszczyk JV, Larsson K, Eriksson E. Subchronic administration of fluoxetine impairs estrous behavior in intact female rats. Neuropsychopharmacology 1998;19:492-8.
212. Mendelson SD, Gorzalka BB. 5-HT1A receptors: Differential involvement in female and male sexual behavior in the rat. Physiol Behav 1986;37:345-51.
213. Mendelson SD, Gorzalka BB. A facilitatory role for serotonin in the sexual behavior of the female rat. Pharmacol Biochem Behav 1985;22:1025-33.
214. Allen DL, Renner KJ, Luine VN. Pargyline-induced increase in serotonin levels: Correlation with inhibition of lordosis in rats. Pharmacol Biochem Behav 1993;45: 837-41.
215. Uphouse L, Caldarola-Pastuszka M. Female sexual behavior following intracerebral infusion of the 5-HT1A agonist, 8-OH-DPAT, into the medial preoptic area. Brain Res 1993;601:203-20.
216. Goldman-Rakic PS. Circuitry of the frontal association cortex and its relevance to dementia. Arch Gerontol Geriatr 1987;6:299-309.
217. Room P, Russchen FT, Groenewegen HJ, Lohman AH. Efferent connections of the prelimibic (area 32) and the infralimbic (area 25) cortices: An anterograde tracing study in the cat. J Comp Neurol 1985;242:40-55.
218. Sesack SR, Pickel VM. Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area. J Comp Neurol 1992;320:145-60.
219. Hajós M, Gartside SE, Varga V, Sharp T. In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: Role of 5-HT1A receptors. Neuropharmacology 2003;34:72-81.
220. Stein DJ, Hemmings S, Moolman-Smook H, Audenaert K. 5-HT2A: Its role in frontally-mediated executive function and related psychopathology. CNS Spectr 2007;12: 512-6.
221. Tanda G, Frau R, Di Chiara G. Local 5HT3 receptors mediate fluoxetine but not desipramine-induced increase of extracellular dopamine in the prefrontal cortex. Psychopharmacology (Berl) 1995;119:15-9.
222. Bortolozzi A, Díaz-Mataix L, Scorza MC, Celada P, Artigas F. The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity. J Neurochem 2005;95:1597-607.
223. Díaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F. Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: Role in atypical antipsychotic action. J Neurosci 2005;25:10831-43.
224. Liu S, Bubar MJ, Lanfranco MF, Hillman GR, Cunningham KA. Serotonin 2C receptor localization in GABA neurons of the rat medial prefrontal cortex: Implications for understanding the neurobiology of addiction. Neuroscience 2007;146:1677-88.
225. Di Matteo V, Di Giovanni G, Pierucci M, Esposito E. Serotonin control of central dopaminergic function: Focus on in vivo microdialysis studies. Prog Brain Res 2008;172:7-44.
226. Best AR, Regehr WG. Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses. J Neurosci 2008;28:6508-15.
227. Kafka MP. Successful antidepressant treatment of nonparaphilic sexual addictions and paraphilias in men. J Clin Psychiatry 1991;52:60-5.
228. Kaplan PM. The use of serotonergic uptake inhibitors in the treatment of premature ejaculation. J Sex Marital Ther 1994;20:321-4.
229. Power-Smith P. Beneficial side-effects from fluoxetine. Br J Psychiatry 1994;16:249-50.
230. Johnson DA. Drug-induced psychiatric disorders. Drugs 1981;22:57-69.
231. Post RM. Cocaine psychoses: A continuum model. Am J Psychiatry 1975;132:225-31.
232. Cowen PJ. Serotonin and depression: Pathophysiological mechanism or marketing myth? Trends Pharmacol Sci 2008;29:433-6.
233. Crowley TJ, Wagner JE, Zerbe G, Macdonald M. Naltrexone-induced dysphoria in former opioid addicts. Am J Psychiatry 1985;142:1081-4.
234. Kline MD. Fluoxetine and anorgasmia. Am J Psychiatry 1989;146:804-5.
235. Ban TA. The role of serendipity in drug discovery. Dialogues Clin Neurosci 2006;8:335-44.
236. Segraves RT, Bari M, Segraves K, Spirnak P. Effect of apomorphine on penile tumescence in men with psychogenic impotence. J Urol 1991;145:1174-5.
237. Proctor JD, Chremos AN, Evans EF, Wasserman AJ. An apomorphine-induced vomiting model for antiemetic studies in man. J Clin Pharmacol 1978;18:95-9.
238. Giuliano F, Allard J, Apomorphine SL. (Uprima): Preclinical and clinical experiences learned from the first central nervous system-acting ED drug. Int J Impot Res 2002;14(1 suppl):S53-6.
239. Borsini F, Ceci A, Bietti G, Donetti A. BIMT 17, a 5-HT1A receptor agonist/5-HT2A receptor antagonist, directly activates postsynaptic 5-HT inhibitory responses in the rat cerebral cortex. Naunyn Schmiedebergs Arch Pharmacol 1995;352:283-90.
240. Borsini F, Evans K, Jason K, Rohde F, Alexander B, Pollentier S. Pharmacology of flibanserin. CNS Drug Rev 2002;8:117-42.
241. Invernizzi RW, Sacchetti G, Parini S, Acconcia S, Samanin R. Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: Role of 5-HT1A receptors. Br J Pharmacol 2003;139:1281-8.
242. Borsini F, Cesana R. Mechanism of action of flibanserin in the learned helplessness paradigm in rats. Eur J Pharmacol 2001;433:81-9.
243. Shapley R, Hawken M, Xing D. The dynamics of visual responses in the primary visual cortex. Prog Brain Res 2007;165:21-32.