Neurobiology of sexual behavior

Current Opinion in Neurobiology

Volumn 9, Issue 6, 1999, Pages 751-758

  Pfaus, James G ^a  

^a and Applied Physiology   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; ANDROGEN; ANDROSTANOLONE; ARGININE; CAPTOPRIL; CLONIDINE; ESTRADIOL; ESTROGEN; FINASTERIDE; FLUOXETINE; LOSARTAN; MONOAMINE; MORPHINE; N METHYL N [7 (1 PYRROLIDINYL) 1 OXASPIRO[4.5]DEC 8 YL]BENZENEACETAMIDE; N(G) METHYLARGININE; NEUROPEPTIDE; NITRIC OXIDE; ORNITHINE DERIVATIVE; OXYTOCIN; PRASTERONE; PROGESTERONE; PROPRANOLOL; SILDENAFIL; TESTOSTERONE; VASOTOCIN DERIVATIVE;

BRAIN MAPPING; BRAIN STEM; COPULATION; EJACULATION; FEMALE; HUMAN; HYPOTHALAMUS; LIMBIC SYSTEM; MALE; MOUSE; NEUROBIOLOGY; NONHUMAN; ORGASM; PENIS ERECTION; PRIORITY JOURNAL; RAT; REVIEW; SEROTONINERGIC SYSTEM; SEXUAL AROUSAL; SEXUAL BEHAVIOR; SEXUAL DYSFUNCTION;

EID: 0032786475     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(99)00034-3     Document Type: Review

References (50)

1. Kippin T.K., Talianakis S., Schattmann L., Bartholomew S., Pfaus J.G. Olfactory conditioning of sexual behavior in the male rat. J Comp Psychol. 112:1998;389-399. This study is the first report of conditioned ejaculatory preference in the male rat. Such preferences are conditioned by pairing neutral odors (e.g. almond, lemon) with copulation, and require ejaculation and a post-ejaculatory interval in the presence of the CS+ odor as the unconditioned stimulus. It uses a triad mating paradigm, in which a male is presented with two sexually receptive females, one with the conditioned odor and one without, to assess copulatory and ejaculatory preferences. The odors can also be paired with access to nonreceptive females to produce inhibitory learning. This paradigm is an important addition to the arsenal of behavioral tests, and will help to reveal the neuroanatomy and pharmacology of excitatory and inhibitory sexual conditioning.
2. Matuszczyk J.V., Larsson K., Eridsson E. Subchronic administration of fluoxetine impairs estrous behavior in intact female rats. Neuropsychopharmacology. 19:1998;492-498.
3. Cantor J., Binik I., Pfaus J.G. Chroinc fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin. Psychopharmacology. 144:1999;355-362. This study demonstrates that daily fluoxetine treatment of male rats produces a short-term inhibition of appetitive sexual behavior, but a longer-term inhibition of ejaculation over a time course similar to that reported in male humans. The inhibition of ejaculation was reversed by a small dose of oxytocin, indicating that decreased oxytocin release before ejaculation may cause the ejaculatory inhibition.
4. Srilatha B., Adaikan P.G., Arulkumaran S., Ng S.C. Sexual dysfunction related to antihypertensive agents: results from the animal model. Int J Impot Res. 11:1999;107-113.
5. Chan P., Liu J.C., Tong Y.C., Chen Y.J., Wang C.C., Tomlinson B., Cheng J.T. Effects of losartan on the sexual behavior of male rats. Pharmacology. 58:1999;132-139.
6. Manzo J., Cruz M.R., Hernandez M.E., Pacheco P., Sachs B.D. Regulation of noncontact erection in rats by gonadal steroids. Horm Behav. 35:1999;264-270. This well-controlled study is notable for showing that androgens but not estrogens stimulate noncontact erections, a homologue of psychogenic sexual arousal in male rats. Because estrogens are capable of stimulating mounting, the results of this study suggest that mounting and erection may be stimulated by two distinct, but interactive, pathways in the brain.
7. 2)5Tyr (Me)2-orn8-vasotocin reduces non-contact penile erections in male rats. Neurosci Lett. 265:1999;171-174. This study suggests that oxytocin and nitric oxide are involved in the stimulation of noncontact erection. This information is important for our understanding of mechanisms involved in the facilitation and inhibition of noncontact erections, and also for the potential pharmacological stimulation of erection in individuals suffering from sexual arousal disorders.
8. Melis M.R., Succu S., Spano M.S., Argiolas A. Morphine injected into the paraventricular nucleus of the hypothalamus prevents noncontact penile erections and impairs copulation: involvement of nitric oxide. Eur J Neurosci. 11:1999;1857-1864.
9. Moses J., Hull E.M. A nitric oxide synthesis inhibitor administered into the medial preoptic area increases seminal emissions in an ex-copula reflex test. Pharmacol Biochem Behav. 63:1999;345-348. This study identifies the mPOA as one area in which nitric oxide stimulates ejaculation.
10. Du J., Hull E.M. Effects of testosterone on neuronal nitric oxide synthase and tyrosine hydroxylase. Brain Res. 836:1999;90-98. Dopamine release decreases in the mPOA following castration but is restored with testosterone treatment. This study shows that nitric oxide synthase, but not tyrosine hydroxylase, in the mPOA is stimulated by testosterone, which may also be the mechanism by which testosterone stimulates dopamine release in the mPOA.
11. Liu Y.C., Sachs B.D. Erectile function in male rats after lesions of the lateral paragigantocellular nucleus. Neurosci Lett. 262:1999;203-206. Male rats with lesions of the lateral paragigantocellular nucleus had more reflexive erections than males with sham lesions, but did not show any change in the copulatory intromission ratio, or in the number of noncontact erections. This suggests that reflexive and noncontact erections are stimulated by two distinct, but perhaps interactive, neural pathways.
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13. ••] are part of an interesting series showing that a single administration of amphetamine, which sensitizes mesolimbic dopamine transmission in male rats, also sensitizes those males to acquire appetitive and consummatory sexual behavior faster than nonsensitized males. The sensitization process also increased the amount of dopamine that was released in the nucleus accumbens during copulation.
14. Arletti R., Benelli A., Cavazzuti E., Scarpetta G., Bertolini A. Stimulating property of Turnera diffusa and Pfaffia paniculata extracts on the sexual behavior of male rats. Psychopharmacology. 143:1999;15-19.
15. Ang H.H., Sim M.K. Eurycoma longifolia increases sexual motivation in sexually naive male rats. Arch Pharm Res. 21:1998;779-781.
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17. Rodriguez-Manzo G. Blockade of the establishment of the sexual inhibition resulting from sexual exhaustion by the Coolidge effect. Behav Brain Res. 100:1999;245-254. This study shows that the inhibition of male sexual behavior induced by copulation to sexual exhaustion can be delayed by presenting males with different females. Thus, the Coolidge effect may work by delaying the induction of sexual inhibition.
18. Rodriguez-Manzo G. Yohimbine interacts with the dopaminergic system to reverse sexual satiation: further evidence for a role of sexual motivation in sexual exhaustion. Eur J Pharmacol. 372:1999;1-8.
19. Riters L.V., Absil P., Balthazart J. Effects of naloxone on the acquisition and expression of appetitive and consummatory sexual behavior in male Japanese quail. Physiol Behav. 66:1999;763-773.
20. Riters L.V., Absil P., Balthazart J. Effects of brain testosterone implants on appetitive and consummatory components of male sexual behavior in Japanese quail. Brain Res Bull. 47:1998;69-79. This study shows that testosterone implants to the mPOA, but not the BNST, can stimulate appetitive and consummatory sexual behavior in male Japanese quail. This is important because it isolates the mPOA of this species as playing a role in both appetitive and consummatory behaviors.
21. Balthazart J., Absil P., Gerard M., Appeltants D., Ball G.F. Appetitive and consummatory male sexual behavior in Japanese quail are differentially regulated by subregions of the preoptic medial nucleus. J Neurosci. 18:1998;6512-6527. This study showed that lesions of discrete subregions of the mPOA in male Japanese quail differentially disrupt appetitive or consummatory sexual behaviors. This is important because it shows how the mPOA is organized for the entire pattern of sexual behavior.
22. Cross E., Roselli C.E. 17beta-estradiol rapidly facilitates chemoinvestigation and mounting in castrated male rats. Am J Physiol. 276:1999;R1346-R1350. This study shows that estradiol can stimulate ano-genital investigation and mounting behavior quickly in short-term castrated male rats, an effect that is too quick to involve a mechanism of gene transcription.
23. Coolen L.M., Wood R.I. Testosterone stimulation of the medial preoptic area and medial amygdala in the control of male hamster sexual behavior: redundancy without amplification. Behav Brain Res. 98:1999;143-153. This study found no difference between the ability of testosterone implants to the mPOA or medial amygdala, or both regions simultaneously, to stimulate copulation in castrated male hamsters. This suggests that true redundancy exists in the brain, and that amplification from one site to another is not required and does not occur for the stimulation of male copulatory behavior by androgens.
24. Wood R.I. Integration of chemosensory and hormonal input in the male Syrian hamster brain. Ann NY Acad Sci. 855:1998;362-372.
25. Matuszewich L., Lorrain D.S., Trujillo R., Dominguez J., Putnam S.K., Hull E.M. Partial antagonism of 8-OH-DPAT's effects on male rat sexual behavior with a D2, but not a 5-HT1A, antagonist. Brain Res. 820:1999;55-62.
26. Rehman J., Kaynan A., Christ G., Valcic M., Maayani S., Melman A. Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor. Brain Res. 821:1999;414-425.
27. Maswood N., Caldarola-Pastuszka M., Uphouse L. Functional integration among 5-hydroxytryptamine receptor families in the control of female sexual behavior. Brain Res. 802:1998;98-103.
28. Neckameyer W.S. Dopamine modulates female sexual receptivity in Drosophila melanogaster. J Neurogenet. 12:1998;101-114. Female Drosophila melanogaster flies were deprived of dopamine by the addition of a tyrosine hydroxylase inhibitor to their diet. These females showed decreases in sexual receptivity toward males, although the males maintained their sexual interest, indicating that attractivity was not altered by the treatment. Replacement with L-DOPA, the precursor eliminated by the inhibition of tyrosine hyrdoxylase, restored sexual receptivity in the females.
29. Frye C.A., Bayon L.E., Pursnani N.K., Purdy R.H. The neurosteroids progesterone and 3alpha,5alpha-THP, enhance sexual motivation, receptivity, and proceptivity in female rats. Brain Res. 808:1998;72-83. This paper reports on the ability of the progesterone metabolite 3α,5α-THP to enhance appetitive and consummatory aspects of sexual behavior in female rats. Previous studies by Frye and colleagues had established that progesterone and this neurosteroid metabolite could facilitate sexual receptivity rapidly in certain brain regions by interaction with GABA/benzodiazepine receptors. Finasteride, an inhibitor of progesterone's metabolism into 3α,5α-THP inhibited the preference of hormonally primed females for sexually vigorous males, and reduced rates of proceptivity and receptivity. This suggests that the ability of progesterone to facilitate appetitive and consummatory sexual behaviors in the female rat may depend on its metabolism in the brain to a progestin that can act on both progesterone and GABA receptors.
30. Pfaus J.G., Smith W.J., Coopersmith C.B. 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. 35:1999;224-240.
31. Brandling-Bennett E.M., Blasberg M.E., Clark A.S. Paced mating behavior in female rats in response to different hormone priming regimens. Horm Behav. 35:1999;144-154.
32. Ramos S.M., DeBold J.F. Protein synthesis in the medial preoptic area is important for the mating-induced decrease in estrus duration in hamsters. Horm Behav. 35:1999;177-185. This fascinating study demonstrates that protein synthesis in the mPOA is required for the well-established ability of vagino-cervical stimulation to induce estrus termination. It is the first study to reveal a region of the brain involved in estrus termination, and its implication of the mPOA has important repercussions for our understanding of the way that genito-sensory stimuli activate 'future events', that is, pathways that will be involved at a later time in the termination of behavior.
33. Romeo R.D., Parfitt D.B., Richardson H.N., Sisk C.L. Pheromones elicit equivalent levels of Fos-immunoreactivity in prepubertal and adult male Syrian hamsters. Horm Behav. 34:1998;48-55. This is another study with important implications. Here, Fos immunocytochemistry was used to mark cells that were activated in juvenile and adult male hamsters following exposure to female hamster vaginal secretions. It was found that pheromonal stimulation induced relatively equal amounts of Fos in the brains of these animals, indicating that the sensory pathways that convey pheromonal information relevant for the stimulation of sexual activity are wired prior to puberty, despite the inability of prepubertal males to initiate copulation. This suggests that androgens do not amplify the sensory impact, but rather connect it to motor programs appropriate for copulation.
34. Kelkliher K.R., Liu Y.C., Baum M.J., Sachs B.D. Neuronal Fos activation in olfactory bulb and forebrain of male rats having erections in the presence of inaccessible estrous females. Neuroscience. 92:1999;1025-1033. This study used Fos to reveal brain regions of male rats that are activated during noncontact erections evoked by bedding that contained female rat estrous odors. Fos was enhanced in males showing noncontact erections in subregions of the nucleus accumbens, anterior and posterior medial amygdala, BNST, and mPOA, but not in olfactory bulb, compared with males that did not show noncontact erections, or males given access to clean bedding.
35. Parfitt D.B., Newman S.W. Fos-immunoreactivity within the extended amygdala is correlated with the onset of sexual satiety. Horm Behav. 34:1998;17-29. This study used Fos to reveal brain areas activated following sexual satiety versus copulation. Fos clusters were found in nuclei within the medial amygdala and BNST in males that ejaculated to satiety on four consecutive tests, versus males that did not copulate. These sites may constitute part of a pathway for sexual inhibition induced by satiety.
36. ••] showing that the sensitization of mesolimbic dopamine release by amphetamine causes male rats to acquire sexual behavior faster. Sensitization of several different dopamine systems by copulation may thus constitute a common mechanism for the acquisition of unconditioned and conditioned sexual responses.
37. Coolen L.M., Peters H.J., Veening J.G. Anatomical interrelationships of the medial preoptic area and other brain regions activated following male sexual behavior: a combined Fos and tract-tracing study. J Comp Neurol. 397:1998;421-435. Fos induction in the mPOA following copulation in male rats was co-labelled with anterograde and retrograde tracers in an effort to determine the functional pathways that relay information to and from the mPOA. Bidirectional connections to the mPOA came from subregions of the BNST, postero-dorsal preoptic nucleus, medial amygdala, and subparafascicular thalamic nucleus.
38. Foidart A., Meddle S.L., Balthazart J. Mating-induced Fos and aromatase are not co-localized in the preoptic area. Neuroreport. 10:1999;907-912.
39. Greco B., Edwards D.A., Michael R.P., Zumpe D., Clancy A.N. Colocalization of androgen receptors and mating-induced Fos immunoreactivity in neurons that project to the central tegmental field in male rats. J Comp Neurol. 408:1999;220-236. Copulation-induced Fos was found co-localized with androgen receptor in the central tegmental field of the midbrain of male rats. Additional retrograde tracing revealed connections to the mPOA, BNST, VMH and medial amygdala. It is possible that androgens act in the central tegmentum to facilitate the transmission of genito-sensory information to forebrain hypothalamic structures.
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43. Honda S., Harada N., Ito S., Takagi Y., Maeda S. Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene. Biochem Biophys Res Commun. 252:1998;445-449. These four studies show the power of transgenic mouse preparations when they are used properly to analyse mechanisms of behavior. Progesterone was found to facilitate lordosis in females with a deletion of the progesterone receptor (PRKO), suggesting that progesterone may act on substrates other than the intracellular progestin receptor to facilitate lordosis. Female mice with a deletion of the α form of the estrogen receptor (ERKO) did not display lordosis following hormone treatment, but instead were highly aggressive toward males that attempted to mount them. These females also lacked parental behavior and were more likely to engage in infanticide. In contrast, ERKO males lacked offensive aggression compared with wild-type males, but both testosterone and dihydrotestosterone were capable of restoring mounting behavior. Although these results suggest that the α form of the estrogen receptor is not necessary for the stimulation of male sexual behavior by androgens in mice, male mice with a deletion of the aromatase gene (ArKO) had longer latencies to initiate sexual activity.
44. Halpern C.T., Udry J.R., Suchindran C. Monthly measures of salivary testosterone predict sexual activity in adolescent males. Arch Sex Behav. 27:1998;445-465. This study showed that testosterone measures from the saliva of heterosexual adolescent men correlated positively with the number of times they initiated sexual contact. Measures of circulating androgens may thus predict sexual contact, although it remains to be determined whether sexual contact led to the increases in androgens.
45. Flynn M.A., Weaver-Osterholtz D., Sharpe-Timms K.L., Allen S., Krause G. Dehydroepiandrosterone replacement in aging humans. J Clin Endocrinol Metab. 84:1999;1527-1533.
46. Sarrel P., Dobay B., Wiita B. Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses. J Reprod Med. 43:1998;847-856. This well-controlled study showed that the combination of estrogen and androgen was more effective than estrogen alone in stimulating sexual desire, arousal and copulation in postmenopausal women. Androgens thus play a key role in sexual desire and satisfaction in human females.
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48. ••] examined cardiovascular and endocrine correlates of sexual orgasm in men and women. Orgasm induced a long-term increase in plasma prolactin levels of both men and women, whereas arousal increased cardiovascular responses in both men and women, but produced small increases in plasma concentrations of luteinizing hormone and testosterone only in women.
49. Blaicher W., Gruber D., Bieglmayer C., Blaicher A.M., Knogler W., Huber J.C. The role of oxytocin in relation to female sexual arousal. Gynecol Obst Invest. 47:1999;125-126.
50. Stoleru S., Gregoire M.C., Gerard D., Decety J., Lafarge E., Cinotti L., Lavenne F., Le Bars D., Vernet-Maury E., Rada H.et al. Neuroanatomical correlates of visually evoked sexual arousal in human males. Arch Sex Behav. 28:1999;1-21. This is the first published study of neuroanatomical activation in human brains following visually evoked sexual arousal. Positron emission tomography (PET) was used to identify activation in human males following exposure to sexually explicit, humorous or emotionally neutral film clips. Sexual arousal was associated with bilateral activation of the inferior temporal cortex, right insular and inferior frontal cortex, and left anterior cingulate cortex. The latter two regions are considered paralimbic and play a role in the processing of sensory information related to motivation and autonomic functions. The degree of activation in these regions also correlated positively with plasma testosterone concentrations. It is expected that more studies of human brain activation by sexual stimuli will follow that utilize both PET and MRI technologies.