Pathways of Sexual Desire
Tóm tắt
Sexual desire is controlled by brain systems involved in sexual excitation and inhibition. Hypoactive sexual desire disorder (HSDD) may result from hypofunctional excitation, hyperfunctional inhibition, or some mix of the two.
This study aimed to identify neurochemical and neuroanatomical systems involved in sexual excitation and inhibition, their role during normal, and hypoactive sexual expressions.
A comprehensive review of the human and animal literature is made, and a theory surrounding the ways that HSDD can be manifested and treated is presented.
Drug effects and neural systems derived largely from rat studies that are involved in the stimulation of sexual desire (excitatory system) vs. the stimulation of sexual reward, sedation, and satiety (inhibitory system).
Brain dopamine systems (incertohypothalamic and mesolimbic) that link the hypothalamus and limbic system appear to form the core of the excitatory system. This system also includes melanocortins, oxytocin, and norepinephrine. Brain opioid, endocannabinoid, and serotonin systems are activated during periods of sexual inhibition, and blunt the ability of excitatory systems to be activated.
Drugs that stimulate the activation of hypothalamic dopamine or that blunt endocannabinoid or serotonin release and/or postsynaptic binding may be effective in stimulating sexual desire in animals and humans. The characterization of how those drugs work will help generate a rational approach to drug development in the treatment of HSDD.
Từ khóa
Tài liệu tham khảo
American Psychiatric Association, 2000, Diagnostic and statistical manual of psychiatric disorders IV-TR (Text Revision)
Robinson, 1993, The neural basis of drug craving: An incentive-sensitization theory of addiction, Brain Res Rev, 18, 247, 10.1016/0165-0173(93)90013-P
Basson, 2002, Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder, J Womens Health Gend Based Med, 11, 367, 10.1089/152460902317586001
Toledano, 2006, The Sexual Arousal and Desire Inventory (SADI): A multidimensional scale to assess sexual arousal and desire, J Sex Med, 3, 853, 10.1111/j.1743-6109.2006.00293.x
Pfaff, 1999, Drive: Neurobiological and molecular mechanisms of sexual motivation, 10.7551/mitpress/2502.001.0001
Pfaus, 2003, What can animal models tell us about human sexual response?, Annu Rev Sex Res, 14, 1
McCall, 2006, Cues resulting in desire for sexual activity in women, J Sex Med, 5, 838, 10.1111/j.1743-6109.2006.00301.x
Kaplan, 1974, The new sex therapy
Masters, 1966, Human sexual response
McClintock, 1984, 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, 14, 1, 10.1016/S0065-3454(08)60298-3
Coria-Avila, 2008, Neurochemical basis of conditioned partner preference in the female rat: I. Disruption by naloxone, Behav Neurosci, 122, 385, 10.1037/0735-7044.122.2.385
Kippin, 2001, The development of olfactory conditioned ejaculatory preferences in the male rat. I. Nature of the unconditioned stimulus, Physiol Behav, 73, 457, 10.1016/S0031-9384(01)00484-X
De Jong, 2007, Oxytocin involvement in SSRI-induced delayed ejaculation: A review of animal studies, J Sex Med, 4, 14, 10.1111/j.1743-6109.2006.00394.x
De Jong, 2005, Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: Comparison of fluvoxamine and paroxetine, Psychopharmacology (Berl), 179, 509, 10.1007/s00213-005-2186-6
Pattij, 2005, Animal models of ejaculatory behavior, Curr Pharm Des, 11, 4069, 10.2174/138161205774913363
Pfaus, 1999, Revisiting the concept of sexual motivation, Annu Rev Sex Res, 10, 120
Erskine, 1989, Solicitation behavior in the estrous female rat: A review, Horm Behav, 23, 473, 10.1016/0018-506X(89)90037-8
Beach, 1976, Sexual attractivity, proceptivity, and receptivity in female mammals, Horm Behav, 7, 105, 10.1016/0018-506X(76)90008-8
Pfaus, 2007, Bremelanotide: An overview of preclinical CNS effects on female sexual function, J Sex Med, 4, 269, 10.1111/j.1743-6109.2007.00610.x
Ågmo, 1990, Reinforcing properties of ejaculation in the male rat: The role of opioids and dopamine, Behav Neurosci, 104, 177, 10.1037/0735-7044.104.1.177
Coria-Avila, 2005, Olfactory conditioned partner preference in the female rat, Behav Neurosci, 119, 716, 10.1037/0735-7044.119.3.716
Kippin, 2004, Opposing roles of the nucleus accumbens and anterior lateral hypothalamic area in the control of sexual behaviour in the male rat, Eur J Neurosci, 19, 698, 10.1111/j.0953-816X.2003.03160.x
Paredes, 2001, Naloxone blocks place preference conditioning after paced mating in female rats, Behav Neurosci, 115, 1363, 10.1037/0735-7044.115.6.1363
Paredes, 1999, What do female rats like about sex? Paced mating, Behav Brain Res, 105, 117, 10.1016/S0166-4328(99)00087-X
Mehrara, 1990, Naloxone disrupts the expression but not the acquisition by male rats of a conditioned place preference response for an oestrous female, Psychopharamacology (Berl), 101, 118, 10.1007/BF02253728
Gray, 1987, The neuropsychology of anxiety
Bancroft, 2000, The dual control model of male sexual response: A theoretical approach to centrally mediated erectile dysfunction, Neurosci Biobehav Rev, 24, 571, 10.1016/S0149-7634(00)00024-5
Perelman, 2006, A new combination treatment for premature ejaculation: A sex therapist’s perspective, J Sex Med, 3, 1004, 10.1111/j.1743-6109.2006.00238.x
Abel, 1980, A review of alcohol’s effects on sex and reproduction, Drug Alcohol Depend, 5, 321, 10.1016/0376-8716(80)90158-1
Castilla, 1999, Drug and alcohol consumption and sexual risk behavior among young adults: Results from a national survey, Drug Alcohol Depend, 56, 47, 10.1016/S0376-8716(99)00008-3
Bancroft, 2003, The relation between mood and sexuality in heterosexual men, Arch Sex Behav, 32, 217, 10.1023/A:1023409516739
Kow, 1988, Transmitter and peptide actions on hypothalamic neurons in vitro: Implications for lordosis, Brain Res Bull, 20, 857, 10.1016/0361-9230(88)90102-5
Parsons, 1982, Hypothalamic protein synthesis essential for the activation of the lordosis reflex in the female rat, Endocrinology, 110, 620, 10.1210/endo-110-2-620
Everitt, 1990, Sexual motivation: A neural and behavioural analysis of the mechanisms underlying appetitive and copulatory responses of male rats, Neurosci Biobehav Rev, 14, 217, 10.1016/S0149-7634(05)80222-2
Kingsberg, 2002, The impact of aging on sexual function in women and their partners, Arch Sex Behav, 31, 431, 10.1023/A:1019844209233
Pfaus, 1999, 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, 35, 224, 10.1006/hbeh.1999.1516
Redouté, 2005, Brain processing of visual sexual stimuli in treated and untreated hypogonadal patients, Psychoneuroendocrinology, 30, 461, 10.1016/j.psyneuen.2004.12.003
Sakuma, 2008, Neural substrates for sexual preference and motivation in the female and male rat, Ann N Y Acad Sci, 1129, 55, 10.1196/annals.1417.009
McCall, 2007, Differences between pre- and postmenopausal women in cues for sexual desire, J Sex Med, 4, 364, 10.1111/j.1743-6109.2006.00421.x
Wylie, 2007, Loss of sexual desire in the postmenopausal woman, J Sex Med, 4, 395, 10.1111/j.1743-6109.2006.00419.x
Corona, 2005, The impotent couple: Low desire, Int J Androl, 28, 46, 10.1111/j.1365-2605.2005.00594.x
Christensen, 1974, Intrahypothalamic implants of testosterone or estradiol and resumption of masculine sexual behavior in long-term castrated male rats, Endocrinology, 95, 984, 10.1210/endo-95-4-984
Södersten, 1976, Sexual behavior in castrated male rats treated with monoamine synthesis inhibitors and testosterone, Pharmacol Biochem Behav, 5, 319, 10.1016/0091-3057(76)90084-8
Smith, 1977, Plasma testosterone and sexual behavior following intracerebral implantation of testosterone propionate in the castrated male rat, Horm Behav, 8, 77, 10.1016/0018-506X(77)90022-8
Beach, 1956, Sexual exhaustion and recovery in the male rat, Q J Exp Psychol, 8, 121, 10.1080/17470215608416811
Larsson, 1956, Conditioning and sexual behavior in the male albino rat, Acta Physiol Gothoburgensia, 1, 1
Fernandez-Guasti, 2003, Sexual behavior reduces hypothalamic androgen receptor immunoreactivity, Psychoneuroendocrinology, 28, 501, 10.1016/S0306-4530(02)00036-7
Bolling, 1939, The estrogen-progesterone induction of mating responses in the spayed female rat, Endocrinology, 25, 359, 10.1210/endo-25-3-359
Jones, 2008, Sexual behavior in ovariectomized Wistar rats following varied doses of testosterone with or without estrogen, and the effects of repeated exposure to testosterone
Stanislaw, 1988, Correlation between sexual desire and menstrual cycle characteristics, Arch Sex Behav, 17, 499, 10.1007/BF01542338
Stuckey, 2008, Female sexual function and dysfunction in the reproductive years: The influence of endogenous and exogenous sex hormones, J Sex Med, 5, 2282, 10.1111/j.1743-6109.2008.00992.x
Wallen, 1984, Periovulatory changes in female sexual behaviour and patterns of ovarian steroid secretion in group-living rhesus monkeys, Horm Behav, 18, 431, 10.1016/0018-506X(84)90028-X
Hampson, 1990, Variations in sex-related cognitive abilities across the menstrual cycle, Brain Cogn, 14, 26, 10.1016/0278-2626(90)90058-V
McCormick, 2001, Menstrual cycle variation in spatial ability: Relation to salivary cortisol levels, Horm Behav, 39, 29, 10.1006/hbeh.2000.1636
Mordecai, 2008, Effects of menstrual cycle phase and oral contraceptive use on verbal memory, Horm Behav, 54, 286, 10.1016/j.yhbeh.2008.03.006
Sherwin, 2003, Estrogen and cognitive functioning in women, Endocr Rev, 24, 133, 10.1210/er.2001-0016
Slob, 1996, Sexual arousability and the menstrual cycle, Psychoneuroendocrinology, 21, 545, 10.1016/0306-4530(95)00058-5
Krug, 2000, Selective influence of the menstrual cycle on perception of stimuli with reproductive significance: An event-related potential study, Psychophysiology, 37, 111, 10.1111/1469-8986.3710111
Gizewski, 2006, There are differences in cerebral activation between females in distinct menstrual phases during viewing of erotic stimuli: A fMRI study, Exp Brain Res, 174, 101, 10.1007/s00221-006-0429-3
Archer, 2006, Effect of estradiol versus estradiol and testosterone on brain-activation patterns in postmenopausal women, Menopause, 13, 528, 10.1097/01.gme.0000188737.46746.cd
Sherwin, 1985, Androgen enhances sexual motivation in females: A prospective, crossover study of sex steroid administration in surgical menopause, Psychosom Med, 47, 339, 10.1097/00006842-198507000-00004
Kingsberg, 2007, Testosterone treatment for hypoactive sexual desire disorder in postmenopausal women, J Sex Med, 4, 227, 10.1111/j.1743-6109.2007.00449.x
Segraves, 2008, Management of hypoactive sexual desire disorder, Adv Psychosom Med, 29, 23, 10.1159/000126622
Hull, 1999, Hormone-neurotransmitter interactions in the control of sexual behavior, Behav Brain Res, 105, 105, 10.1016/S0166-4328(99)00086-8
Roth, 1995, Biochemical pharmacology of midbrain dopamine neurons. In, Psychopharmacology: The fourth generation of progress, 227
Moore, 1995, Dopaminergic neuronal systems in the hypothalamus. In, Psychopharmacology: The fourth generation of progress, 245
Blackburn, 1992, Dopamine functions in appetitive and defensive behaviours, Prog Neurobiol, 39, 247, 10.1016/0301-0082(92)90018-A
Hoshina, 1994, Axon-sparing lesion of the preoptic area enhances receptivity and diminishes proceptivity among components of female rat sexual behavior, Behav Brain Res, 61, 197, 10.1016/0166-4328(94)90160-0
Paredes, 1997, Role of the medial preoptic area/anterior hypothalamus in the control of masculine sexual behavior, Annu Rev Sex Res, 8, 68
Liu, 1998, Sexual behavior in male rats after radiofrequency or dopamine-depleting lesions in nucleus accumbens, Pharmacol Biochem Behav, 60, 585, 10.1016/S0091-3057(98)00022-7
Guarraci, 2002, Effects of ibotenic acid lesions of the nucleus accumbens on paced mating behavior in the female rat, Behav Neurosci, 116, 568, 10.1037/0735-7044.116.4.568
Hull, 1989, D2/D1 ratio in the medial preoptic area affects copulation of male rats, J Pharmacol Exp Ther, 251, 422
Hyyppä, 1970, The activating effect of L-dopa treatment on sexual functions and its experimental background, Acta Neurol Scand, 46, 223
Malmnäs, 1977, Dopaminergic reversal of the decline after castration of rat copulatory behaviour, J Endocrinol, 73, 187, 10.1677/joe.0.0730187
Malmnäs, 1976, The significance of dopamine, versus other catecholamines, for L-dopa induced facilitation of sexual behavior in the castrated male rat, Pharmacol Biochem Behav, 4, 521, 10.1016/0091-3057(76)90191-X
Heaton, 1991, The characterization of a bio-assay of erectile function in a rat model, J Urol, 145, 1099, 10.1016/S0022-5347(17)38543-9
Lal, 1984, Effect of apomorphine, a dopamine receptor agonist, on penile tumescence in normal subjects, Prog Neuropsychopharmacol Biol Psychiatry, 8, 695, 10.1016/0278-5846(84)90040-X
Foreman, 1987, Effects of D2-dopaminergic receptor stimulation on male rat sexual behavior, J Neural Transm, 68, 153, 10.1007/BF02098495
McIntosh, 1984, Brain monoaminergic control of male reproductive behavior. II. Dopamine and the post-ejaculatory refractory period, Behav Brain Res, 12, 267, 10.1016/0166-4328(84)90152-9
Pfaus, 1991, Role of dopamine in anticipatory and consummatory aspects of sexual behavior in the male rat, Behav Neurosci, 105, 727, 10.1037/0735-7044.105.5.727
Pfaus, 1989, Differential effects of dopamine receptor antagonists on the sexual behavior of male rats, Psychopharmacology (Berl), 98, 363, 10.1007/BF00451688
Grierson, 1988, The effect of selective D1 and D2 dopaminergic agents on sexual receptivity in the female rat, Neuropharmacology, 27, 181, 10.1016/0028-3908(88)90169-4
Becker, 1990, Direct effect of 17 beta-estradiol on striatum: Sex differences in dopamine release, Synapse, 5, 157, 10.1002/syn.890050211
Sanderson, 2008, Preoptic neuronal nitric oxide synthase induction by testosterone is consistent with a role in gating male copulatory behavior, Eur J Neurosci, 27, 183, 10.1111/j.1460-9568.2007.05989.x
Sato, 2005, 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, 1043, 205, 10.1016/j.brainres.2005.02.074
Pfaus, 2001, Conditioning and sexual behavior: A review, Horm Behav, 40, 291, 10.1006/hbeh.2001.1686
Meisel, 1994, The physiology of male reproducation, The physiology of reproduction, 3
Fiorino, 1997, Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect in male rats, J Neurosci, 17, 4849, 10.1523/JNEUROSCI.17-12-04849.1997
Moore, 1979, Central catecholamine neuron systems: Anatomy and physiology of the norepinephrine and epinephrine systems, Annu Rev Neurosci, 2, 113, 10.1146/annurev.ne.02.030179.000553
Green, 1957, 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, 108, 505, 10.1002/cne.901080308
Cooper, 1991, The biochemical basis of neuropharmacology
Ramírez, 1982, Effect of estrogen and progesterone priming on the uptake and release of serotonin and noradrenaline from the ventromedial hypothalamus, Acta Physiol Lat Am, 32, 313
Fernández-Guasti, 1985, Potentiative action of alpha- and beta-adrenergic receptor stimulation in inducing lordosis behavior, Pharmacol Biochem Behav, 22, 613, 10.1016/0091-3057(85)90283-7
Weiland, 1987, Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions, Endocrinology, 121, 1751, 10.1210/endo-121-5-1751
Etgen, 1990, Intrahypothalamic implants of noradrenergic antagonists disrupt lordosis behavior in female rats, Physiol Behav, 48, 31, 10.1016/0031-9384(90)90256-4
Malmnäs, 1973, Monoaminergic influence on testosterone-activated copulatory behavior in the castrated male rat, Acta Physiol Scand, 395, 1
Clark, 1990, Clonidine suppresses copulatory behavior and erectile reflexes in male rats: Lack of effect of naloxone pretreatment, Neuroendocrinology, 51, 357, 10.1159/000125361
Meston, 1997, Inhibition of physiological and subjective sexual arousal in women by clonidine, Psychosom Med, 59, 399, 10.1097/00006842-199707000-00010
Allard, 2001, Central nervous system agents in the treatment of erectile dysfunction: How do they work?, Curr Urol Rep, 2, 488, 10.1007/s11934-001-0044-6
Rodríguez-Manzo, 1994, Reversal of sexual exhaustion by serotonergic and noradrenergic agents, Behav Brain Res, 62, 127, 10.1016/0166-4328(94)90019-1
Clark, 1995, Sexual arousal and performance are modified by adrenergic-neuropeptide-steroid interactions. In, The pharmacology of sexual function and dysfunction, 55
McIntosh, 1984, Brain monoaminergic control of male reproductive behavior. III. Norepinephrine and the post-ejaculatory refractory period, Behav Brain Res, 12, 275, 10.1016/0166-4328(84)90153-0
Voisey, 2003, Melanocortins and their receptors and antagonists, Curr Drug Targets, 4, 586, 10.2174/1389450033490858
Oosterom, 1999, Conformation of the core sequence in melanocortin peptides directs selectivity for the melanocortin MC3 and MC4 receptors, J Biol Chem, 274, 16853, 10.1074/jbc.274.24.16853
Heisler, 2003, Central serotonin and melanocortin pathways regulating energy homeostasis, Ann N Y Acad Sci, 994, 169, 10.1111/j.1749-6632.2003.tb03177.x
O’Donohue, 1982, The opiomelanotropinergic neuronal and endocrine system, Peptides, 3, 353, 10.1016/0196-9781(82)90098-5
Medina, 1998, 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, 19, 1309, 10.1016/S0196-9781(98)00093-X
Wilson, 1991, Interaction of estradiol, alpha-melanocyte-stimulating hormone, and dopamine in the regulation of sexual receptivity in the female rat, Neuroendocrinology, 54, 14, 10.1159/000125845
Diamond, 2004, 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, 16, 51, 10.1038/sj.ijir.3901139
Rosen, 2004, 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, 16, 135, 10.1038/sj.ijir.3901200
Hadley, 2005, Discovery that a melanocortin regulates sexual functions in male and female humans, Peptides, 26, 1687, 10.1016/j.peptides.2005.01.023
Diamond, 2006, 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, 3, 628, 10.1111/j.1743-6109.2006.00268.x
Pfaus, 2004, Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist, Proc Natl Acad Sci U S A, 101, 10201, 10.1073/pnas.0400491101
Rössler, 2006, The melanocortin agonist, melanotanII, enhances proceptive sexual behaviors in the female rat, Pharmacol Biochem Behav, 85, 514, 10.1016/j.pbb.2006.09.023
Carter, 1992, Oxytocin and social bonding, Ann N Y Acad Sci, 652, 204, 10.1111/j.1749-6632.1992.tb34356.x
Caldwell, 1989, Medial preoptic area oxytocin and female sexual receptivity, Behav Neurosci, 103, 655, 10.1037/0735-7044.103.3.655
Schulze, 1991, Oxytocin effects on lordosis frequency and lordosis duration following infusion into the medial pre-optic area and ventromedial hypothalamus of female rats, Neuropeptides, 18, 99, 10.1016/0143-4179(91)90008-7
Kita, 2006, An activation of parvocellular oxytocinergic neurons in the paraventricular nucleus in oxytocin-induced yawning and penile erection, Neurosci Res, 54, 269, 10.1016/j.neures.2005.12.005
Cantor, 1999, Chronic fluoxetine inhibits sexual behavior in the male rat: Reversal with oxytocin, Psychopharmacology (Berl), 144, 355, 10.1007/s002130051018
Hillegaart, 1998, Sexual motivation promotes oxytocin secretion in male rats, Peptides, 19, 39, 10.1016/S0196-9781(97)00250-7
Ménard, 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
Succu, 2007, 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, 52, 1034, 10.1016/j.neuropharm.2006.10.019
Saphier, 1986, Electrophysiology of limbic forebrain and paraventricular nucleus connections, Brain Res Bull, 17, 743, 10.1016/0361-9230(86)90085-7
Kinsey, 1948, Sexual behavior in the human male
Anastasopoulos, 1958, Hypersexuality, change of character, sleep disorders & acute dementia in a tumor of the right temporal lobe, Psychiatr Neurol (Basel), 136, 85, 10.1159/000139551
Chow, 1999, Neuropsychiatry: Clinical assessment and approach to diagnosis, Comprehensive texbook of psychiatry, 221
Góscínski, 1997, The Kluver-Bucy syndrome, J Neurosurg Sci, 41, 269
Kanowski, 1971, Hypersexuality in relation to partial Klüver-Bucy syndrome (author’s transl), J Neurovisc Relat, 10, 504
Robbins, 2007, Shifting and stopping: Fronto-striatal substrates, neurochemical modulation, and clinical implications, Philos Trans R Soc Lond B Biol Sci, 362, 917, 10.1098/rstb.2007.2097
Robbins, 1996, Dissociating executive functions of the prefrontal cortex, Philos Trans R Soc Lond B Biol Sci, 351, 1463, 10.1098/rstb.1996.0131
Andrés, 2001, Supervisory attentional system in patients with focal frontal lesions, Clin J Exp Neuropsychol, 23, 225, 10.1076/jcen.23.2.225.1212
Tamm, 2002, Maturation of brain function associated with response inhibition, J Am Acad Child Adolesc Psychiatry, 41, 1231, 10.1097/00004583-200210000-00013
Winn, 1998, Frontal syndrome as a consequence of lesions in the pedunculopontine tegmental nucleus: A short theoretical review, Brain Res Bull, 47, 551, 10.1016/S0361-9230(98)00136-1
Pfaus, 1989, Alcohol inhibits and disinhibits sexual behavior in the male rat, Psychobiology, 17, 195, 10.3758/BF03337836
Perper, 1985, Sex signals: The biology of love
Toates, 1992, Motivational systems
Pfaus, 1987, Opioids and sexual behavior, Neurosci Biobehav Rev, 11, 1, 10.1016/S0149-7634(87)80002-7
Chessick, 1960, The “pharmacogenic orgasm” in the drug addict, Arch Gen Psychiat, 3, 545, 10.1001/archpsyc.1960.01710050095010
Whipple, 1985, Elevation of pain threshold by vaginal stimulation in women, Pain, 21, 357, 10.1016/0304-3959(85)90164-2
Szechtman, 1981, Sexual behavior decreases pain sensitivity and stimulated endogenous opioids in male rats, Eur J Pharmacol, 70, 279, 10.1016/0014-2999(81)90161-8
Rodríguez-Manzo, 1995, Opioid antagonists and the sexual satiation phenomenon, Psychopharmacology (Berl), 122, 131, 10.1007/BF02246087
Ismail, 2008, Context-dependent acquisition of copulatory behavior in the male rat: Role of female availability, Behav Neurosci, 122, 991, 10.1037/a0012831
Patterson, 1983, Classification of opioid receptors, Br Med Bull, 39, 31, 10.1093/oxfordjournals.bmb.a071787
Band, 1990, Morphine and dynorphin(1-13) microinjected into the medial preoptic area and nucleus accumbens: Effects on sexual behavior in male rats, Brain Res, 524, 77, 10.1016/0006-8993(90)90494-V
Hughes, 1987, 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, 23, 1063, 10.1016/0306-4522(87)90181-3
Matuszewich, 1995, Effects of morphiceptin in the medial preoptic area on male sexual behavior, Psychopharmacology (Berl), 122, 330, 10.1007/BF02246262
Acosta-Martinez, 2002, Activation of mu-opioid receptors inhibits lordosis behavior in estrogen and progesterone-primed female rats, Horm Behav, 41, 88, 10.1006/hbeh.2001.1741
Coolen, 2004, Activation of mu opioid receptors in the medial preoptic area following copulation in male rats, Neuroscience, 124, 11, 10.1016/j.neuroscience.2003.10.045
Ågmo, 1993, Sexual reinforcement is blocked by infusion of naloxone into the medial preoptic area, Behav Neurosci, 107, 812, 10.1037/0735-7044.107.5.812
Rodríguez-Manzo, 2002, Evidence for changes in brain enkephalin contents associated to male rat sexual activity, Behav Brain Res, 131, 47, 10.1016/S0166-4328(01)00371-0
Mitchell, 1990, Facilitation of sexual behaviors in the male rat associated with intra-VTA injections of opiates, Pharmacol Biochem Behav, 35, 643, 10.1016/0091-3057(90)90302-X
Mitchell, 1992, Mesolimbic dopamine release elicited by activation of the accessory olfactory system: A high-speed chronoamperometric study, Neurosci Lett, 140, 81, 10.1016/0304-3940(92)90687-3
Van Furth, 1996, Sexual motivation: Involvement of endogenous opioids in the ventral tegmental area, Brain Res, 729, 20, 10.1016/0006-8993(96)00225-9
Kalivas, 1987, Enkephalin release into the ventral tegmental area in response to stress: Modulation of mesocorticolimbic dopamine, Brain Res, 414, 339, 10.1016/0006-8993(87)90015-1
Yoshida, 1993, Facilitatory modulation of mesolimbic dopamine neuronal activity by a mu-opioid agonist and nicotine as examined with in vivo microdialysis, Brain Res, 624, 277, 10.1016/0006-8993(93)90087-4
Bergevin, 2002, Presynaptic mu-opioid receptors regulate a late step of the secretory process in rat ventral tegmental area GABAergic neurons, Neuropharmacology, 42, 1065, 10.1016/S0028-3908(02)00061-8
Acosta-Martinez, 2002, The role of delta-opioid receptors in estrogen facilitation of lordosis behavior, Behav Brain Res, 136, 93, 10.1016/S0166-4328(02)00103-1
Pfaus, 1992, Mu-, delta-, and kappa-opioid receptor agonists selectively modulate sexual behaviors in the female rat: Differential dependence on progesterone, Horm Behav, 26, 457, 10.1016/0018-506X(92)90014-M
Sinchak, 2004, Medial preoptic area delta-opioid receptors inhibit lordosis, Behav Brain Res, 155, 301, 10.1016/j.bbr.2004.05.001
McCarthy, 1990, Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area, Brain Res, 507, 40, 10.1016/0006-8993(90)90519-H
Devidze, 2008, Presynaptic actions of opioid receptor agonists in ventromedial hypothalamic neurons in estrogen- and oil-treated female mice, Neuroscience, 152, 942, 10.1016/j.neuroscience.2008.01.033
Lauber, 1990, Estradiol induction of proenkephalin messenger RNA in hypothalamus: Dose-response and relation to reproductive behavior in the female rat, Brain Res Mol Brain Res, 8, 47, 10.1016/0169-328X(90)90008-2
Sinchak, 2001, Progesterone blockade of estrogen activation of mu-opioid receptors regulates reproductive behavior, J Neurosci, 21, 5723, 10.1523/JNEUROSCI.21-15-05723.2001
Rodríguez-Manzo, 1999, Anxiolytic-like effect of ejaculation under various sexual behavior conditions in the male rat, Physiol Behav, 67, 651, 10.1016/S0031-9384(99)00119-5
Pazos, 2005, Functional neuroanatomy of the endocannabinoid system, Pharmacol Biochem Behav, 81, 239, 10.1016/j.pbb.2005.01.030
Pars, 1977, Potential therapeutic agents derived from the cannabinoid nucleus, Adv Drug Res, 11, 97
Mani, 2001, Progesterone recepetor and dopamine receptors are required in Delta-9-tetrahydrocannabinol modulation of sexual receptivity in female rats, Proc Natl Acad Sci USA, 98, 1248
Baker, 2003, The therapeutic potential of cannabis, Lancet Neurol, 2, 291, 10.1016/S1474-4422(03)00381-8
Crenshaw, 1996, Sexual pharmacology: Drugs that affect sexual function
Martinez-Gonzalez, 2004, Oleamide and anandamide effects on food intake and sexual behavior of rats, Neurosci Lett, 364, 1, 10.1016/j.neulet.2004.03.080
Navarro, 1993, An acute dose of delta 9-tetrahydrocannabinol affects behavioral and neurochemical indices of mesolimbic dopaminergic activity, Behav Brain Res, 57, 37, 10.1016/0166-4328(93)90059-Y
Gorzalka, 2008, Endocannabinoid modulation of male sexual behavior, Psychopharmacology (Berl), 198, 479, 10.1007/s00213-007-0901-1
Mellis, 2004, Antagonism of CB 1 receptors in the paraventricular nucleus of male rats induces penile erection, Neurosci Lett, 359, 17, 10.1016/j.neulet.2004.01.025
Succu, 2006, 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, 169, 274, 10.1016/j.bbr.2006.01.017
Turley, 1980, Delta-9-Tetrahydrocannabinol stimulates receptive and proceptive sexual behaviors in female hamsters, Horm Behav, 14, 65
Ferrari, 2000, Inhibitory effects of the cannabinoid agonist HU 210 on rat sexual behavior, Physiol Behav, 69, 547, 10.1016/S0031-9384(00)00214-6
López, 2009, Cannabinoid receptor antagonism, Pharmacol Biochem Behav, 92, 17, 10.1016/j.pbb.2008.10.004
Bradshaw, 2006, Sex and hormonal cycle differences in rat brain levels of pain-related cannabimimetic lipid mediators, Am J Physiol Regul Integr Comp Physiol, 291, 349, 10.1152/ajpregu.00933.2005
Gonzalez, 2000, Sex steroid influence on cannabinoid CB(1) receptor mRNA and endocannabinoid levels in the anterior pituitary gland, Biochem Biophys Res Commun, 270, 260, 10.1006/bbrc.2000.2406
Blundell, 1986, Serotonin manipulations and the structure of feeding behaviour, Appetite, 7, 39, 10.1016/S0195-6663(86)80051-4
Meyerson, 1964, The effect of neuropharmacological agents on hormone-activated estrus behaviour in ovariectomised rats, Arch Int Pharmacodyn Ther, 150, 4
Dalló, 1977, Effect of two brain serotonin depletors on the sexual behavior of male rats, Pol J Pharmacol Pharm, 29, 247
McIntosh, 1984, Brain monoaminergic control of male reproductive behavior. I. Serotonin and the post-ejaculatory refractory period, Behav Brain Res, 12, 255, 10.1016/0166-4328(84)90151-7
Marson, 1994, Serotonergic neurotoxic lesions facilitate male sexual reflexes, Pharmacol Biochem Behav, 47, 883, 10.1016/0091-3057(94)90292-5
Vega Matuszcyk, 1998, The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats, Pharmacol Biochem Behav, 60, 527, 10.1016/S0091-3057(98)00010-0
Mendelson, 1992, A review and reevaluation of the role of serotonin in the modulation of lordosis behavior in the female rat, Neurosci Biobehav Rev, 16, 309, 10.1016/S0149-7634(05)80204-0
Bradshaw, 1982, Dissociation of the effects of gonadal steroids on brain serotonin metabolism and sexual behavior in the male rat, Neuroendocrinology, 34, 38, 10.1159/000123275
Hoyer, 1996, Classification and nomenclature of 5-HT receptors: A comment on current issues, Behav Brain Res, 73, 263, 10.1016/0166-4328(96)00109-X
Ågmo, 1989, Naloxone inhibits the facilitatory effects of 8-OH-DPAT on male rat sexual behaviour, Eur J Pharmacol, 166, 115, 10.1016/0014-2999(89)90691-2
Ahlenius, 1981, Effects of a new type of 5-HT receptor agonist on male rat sexual behavior, Pharmacol Biochem Behav, 15, 785, 10.1016/0091-3057(81)90023-X
Schnur, 1989, A component analysis of the effects of DPAT on male rat sexual behavior, Physiol Behav, 45, 897, 10.1016/0031-9384(89)90212-6
Camacho, 2007, Facilitation of ejaculation induced by 8-OH-DPAT does not produce conditioned place preference in male rats, Behav Neurosci, 121, 579, 10.1037/0735-7044.121.3.579
Fernández-Guasti, 2003, Pharmacological and physiological aspects of sexual exhaustion in male rats, Scand J Psychol, 44, 257, 10.1111/1467-9450.00343
Fernández-Guasti, 1997, 8-OH-DPAT and male rat sexual behavior: Partial blockade by noradrenergic lesion and sexual exhaustion, Pharmacol Biochem Behav, 56, 111, 10.1016/S0091-3057(96)00165-7
Klint, 1992, 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, 212, 241, 10.1016/0014-2999(92)90336-3
Watson, 1991, DOI-induced inhibition of copulatory behavior in male rats: Reversal by 5-HT2 antagonists, Pharmacol Biochem Behav, 39, 605, 10.1016/0091-3057(91)90135-O
Paredes, 2000, Serotonin and sexual behavior in the male rabbit, J Neural Transm, 107, 767, 10.1007/s007020070057
Yells, 1994, Fluoxetine-induced inhibition of male rat copulatory behavior: Modification by lesions of the nucleus paragigantocellularis, Pharmacol Biochem Behav, 49, 121, 10.1016/0091-3057(94)90465-0
Beitz, 1982, The nuclei of origin of brainstem serotonergic projections to the rodent spinal trigeminal nucleus, Neurosci Lett, 32, 223, 10.1016/0304-3940(82)90297-X
Fernández-Guasti, 1992, Stimulation of 5-HT1A and 5-HT1B receptors in brain regions and its effects on male rat sexual behaviour, Eur J Pharmacol, 210, 121, 10.1016/0014-2999(92)90662-N
Lorrain, 1998, 8-OH-DPAT influences extracellular levels of serotonin and dopamine in the medial preoptic area of male rats, Brain Res, 790, 217, 10.1016/S0006-8993(98)00065-1
Damsma, 1992, Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: Comparison with novelty and locomotion, Behav Neurosci, 106, 181, 10.1037/0735-7044.106.1.181
Lorrain, 1997, Extracellular serotonin in the lateral hypothalamic area is increased during the postejaculatory interval and impairs copulation in male rats, J Neurosci, 17, 9361, 10.1523/JNEUROSCI.17-23-09361.1997
Lorrain, 1999, Lateral hypothalamic serotonin inhibits nucleus accumbens dopamine: Implications for sexual satiety, J Neurosci, 19, 7648, 10.1523/JNEUROSCI.19-17-07648.1999
Sarkar, 2008, Subchronic treatment with fluoxetine attenuates the effects of acute fluoxetine on female rats’ sexual behavior, Brain Res, 1190, 56, 10.1016/j.brainres.2007.11.033
Matuszczyk, 1998, Subchronic administration of fluoxetine impairs estrous behavior in intact female rats, Neuropsychopharmacology, 19, 492, 10.1016/S0893-133X(98)00040-2
Mendelson, 1986, 5-HT1A receptors: Differential involvement in female and male sexual behavior in the rat, Physiol Behav, 37, 345, 10.1016/0031-9384(86)90244-1
Mendelson, 1985, A facilitatory role for serotonin in the sexual behavior of the female rat, Pharmacol Biochem Behav, 22, 1025, 10.1016/0091-3057(85)90313-2
Allen, 1993, Pargyline-induced increase in serotonin levels: Correlation with inhibition of lordosis in rats, Pharmacol Biochem Behav, 45, 837, 10.1016/0091-3057(93)90129-H
Uphouse, 1993, Female sexual behavior following intracerebral infusion of the 5-HT1A agonist, 8-OH-DPAT, into the medial preoptic area, Brain Res, 601, 203, 10.1016/0006-8993(93)91711-Z
Goldman-Rakic, 1987, Circuitry of the frontal association cortex and its relevance to dementia, Arch Gerontol Geriatr, 6, 299, 10.1016/0167-4943(87)90029-X
Room, 1985, Efferent connections of the prelimibic (area 32) and the infralimbic (area 25) cortices: An anterograde tracing study in the cat, J Comp Neurol, 242, 40, 10.1002/cne.902420104
Sesack, 1992, 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, 320, 145, 10.1002/cne.903200202
Hajós, 2003, In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: Role of 5-HT1A receptors, Neuropharmacology, 34, 72, 10.1016/S0028-3908(03)00139-4
Stein, 2007, 5-HT2A: Its role in frontally-mediated executive function and related psychopathology, CNS Spectr, 12, 512, 10.1017/S1092852900021246
Tanda, 1995, Local 5HT3 receptors mediate fluoxetine but not desipramine-induced increase of extracellular dopamine in the prefrontal cortex, Psychopharmacology (Berl), 119, 15, 10.1007/BF02246048
Bortolozzi, 2005, The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity, J Neurochem, 95, 1597, 10.1111/j.1471-4159.2005.03485.x
Díaz-Mataix, 2005, Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: Role in atypical antipsychotic action, J Neurosci, 25, 10831, 10.1523/JNEUROSCI.2999-05.2005
Liu, 2007, Serotonin 2C receptor localization in GABA neurons of the rat medial prefrontal cortex: Implications for understanding the neurobiology of addiction, Neuroscience, 146, 1677, 10.1016/j.neuroscience.2007.02.064
Di Matteo, 2008, Serotonin control of central dopaminergic function: Focus on in vivo microdialysis studies, Prog Brain Res, 172, 7, 10.1016/S0079-6123(08)00902-3
Best, 2008, Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses, J Neurosci, 28, 6508, 10.1523/JNEUROSCI.0678-08.2008
Kafka, 1991, Successful antidepressant treatment of nonparaphilic sexual addictions and paraphilias in men, J Clin Psychiatry, 52, 60
Kaplan, 1994, The use of serotonergic uptake inhibitors in the treatment of premature ejaculation, J Sex Marital Ther, 20, 321, 10.1080/00926239408404382
Power-Smith, 1994, Beneficial side-effects from fluoxetine, Br J Psychiatry, 16, 249, 10.1192/bjp.164.2.249
Cowen, 2008, Serotonin and depression: Pathophysiological mechanism or marketing myth?, Trends Pharmacol Sci, 29, 433, 10.1016/j.tips.2008.05.004
Crowley, 1985, Naltrexone-induced dysphoria in former opioid addicts, Am J Psychiatry, 142, 1081, 10.1176/ajp.142.9.1081
Ban, 2006, The role of serendipity in drug discovery, Dialogues Clin Neurosci, 8, 335, 10.31887/DCNS.2006.8.3/tban
Segraves, 1991, Effect of apomorphine on penile tumescence in men with psychogenic impotence, J Urol, 145, 1174, 10.1016/S0022-5347(17)38565-8
Proctor, 1978, An apomorphine-induced vomiting model for antiemetic studies in man, J Clin Pharmacol, 18, 95, 10.1002/j.1552-4604.1978.tb02427.x
Giuliano, 2002, Uprima): Preclinical and clinical experiences learned from the first central nervous system-acting ED drug, Int J Impot Res, 14, S53, 10.1038/sj.ijir.3900806
Borsini, 1995, 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, 352, 283
Borsini, 2002, Pharmacology of flibanserin, CNS Drug Rev, 8, 117, 10.1111/j.1527-3458.2002.tb00219.x
Invernizzi, 2003, 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, 139, 1281, 10.1038/sj.bjp.0705341
Borsini, 2001, Mechanism of action of flibanserin in the learned helplessness paradigm in rats, Eur J Pharmacol, 433, 81, 10.1016/S0014-2999(01)01495-9