Abstract
Rationale
Lycium barbarum polysaccharide (LBP) is known to promote reproductive functions. However, its role in noncontact erection (NCE) of penis initiated by brain regions including medial preoptic area (MPOA) and paraventricular nucleus (PVN) regions responsible for sexual behavior has not been investigated.
Objectives
Therefore, this study initially investigated the effects of LBP on male sexual function, and subsequently, the mechanistic insight was investigated through assessing the expression of neuronal nitric oxide synthase (nNOS) in the MPOA and PVN.
Methods
The adult male rats were treated with 100 mg/kg of LBP or vehicle by oral gavage. Before and after 14 days of treatment, copulatory behavior and noncontact erection (NCE) were recorded. After the last behavioral test, the brain was isolated to measure nNOS expression in the MPOA and PVN.
Results
Data showed that LBP treatment significantly increased both the frequencies of intromission as well as ejaculation, compared to the control group. Whereas, a reduced post-ejaculatory interval was observed compared to same group on day 0. Furthermore, the treatment led to an increased intromission ratio, inter-intromission interval, and the number of MPOA nNOS-immunoreactive cells (nNOS-ir). Additionally, a significantly positive correlation between ejaculation frequency and MPOA nNOS-ir cells was recorded. Of note, LBP treatment had no effects on NCE and PVN nNOS-ir expression.
Conclusion
These findings suggest that LBP enhances sexual behavior through increased nNOS expression in the MPOA in male rats.
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References
Ackerman AE, Lange GM, Clemens LG (1997) Effects of paraventricular lesions on sex behavior and seminal emission in male rats. Physiol Behav 63:49–53
Agmo A (1997) Male rat sexual behavior. Brain research Brain research protocols 1:203–209
Agmo A, Villalpando A, Picker Z, Fernandez H (1995) Lesions of the medial prefrontal cortex and sexual behavior in the male rat. Brain Res 696:177–186
Andersson KE (2001) Pharmacology of penile erection. Pharmacol Rre 53:417–450
Argiolas A (1994) Nitric oxide is a central mediator of penile erection. Neuropharmacology 33:1339–1344
Argiolas A, Melis MR (2005) Central control of penile erection: role of the paraventricular nucleus of the hypothalamus. Prog Neurobiol 76:1–21
Beach FA (1956) Characteristic of masculine “sex drive”. In: Jones MR. (ed) Nebraska Symposium on Motivation, Press Lincoln, pp 1–31
Benelli A, Bertolini A, Poggioli R, Cavazzuti E, Calza L, Giardino L, Arletti R (1995) Nitric oxide is involved in male sexual behavior of rats. Eur J Pharmacol 294:505–510
Bialy M, Beck J, Abramczyk P, Trzebski A, Przybylski J (1996) Sexual behavior in male rats after nitric oxide synthesis inhibition. Physiol Behav 60:139–143
Bo R, Zheng S, Xing J, Luo L, Niu Y, Huang Y, Liu Z, Hu Y, Liu J, Wu Y, Wang D (2016) The immunological activity of Lycium barbarum polysaccharides liposome in vitro and adjuvanticity against PCV2 in vivo. Int J Biol Macromol 85:294–301
Brackett NL, Iuvone PM, Edwards DA (1986) Midbrain lesions, dopamine and male sexual behavior. Behav Brain Res 20:231–240
Carnes J, de Larramendi CH, Ferrer A, Huertas AJ, Lopez-Matas MA, Pagan JA, Navarro LA, Garcia-Abujeta JL, Vicario S, Pena M (2013) Recently introduced foods as new allergenic sources: sensitisation to Goji berries (Lycium barbarum). Food Chem 137:130–135
Cheng D, Kong H (2011) The effect of Lycium barbarum polysaccharide on alcohol-induced oxidative stress in rats. Molecules 16:2542–2550
Dominguez JM, Brann JH, Gil M, Hull EM (2006) Sexual experience increases nitric oxide synthase in the medial preoptic area of male rats. Behav Neurosci 120:1389–1394
Dong JZ, Yang JJ, Wang Y (2008) Resources of Lycium species and related research progress. Zhongguo Zhong Yao Za Zhi 33:2020–2027
Du J, Hull EM (1999) Effects of testosterone on neuronal nitric oxide synthase and tyrosine hydroxylase. Brain Res 836:90–98
Edwards DA, Einhorn LC (1986) Preoptic and midbrain control of sexual motivation. Physiol Behav 37:329–335
Elabbady A, Hassouna MM, Elhilali M (1995) Apomorphine versus mating behavior in testing erectile capabilities of diabetic rats. Urology 45:715–719
Escrig A, Marin R, Abreu P, Gonzalez-Mora JL, Mas M (2002) Changes in mating behavior, erectile function, and nitric oxide levels in penile corpora cavernosa in streptozotocin-diabetic rats. Biol Rreprod 66:185–189
Everitt BJ (1990) Sexual motivation: a neural and behavioural analysis of the mechanisms underlying appetitive and copulatory responses of male rats. Neurosci Biobehav Rev 14:217–232
Ferraz MM, Quintella SL, Parcial AL, Ferraz MR (2016) The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior. Pharmacol Biochem Behav 146-147:13–20
Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837
Fouche G, Afolayan AJ, Wintola OA, Khorombi TE, Senabe J (2015) Effect of the aqueous extract of the aerial parts of Monsonia angustifolia E. Mey. Ex A. Rich., on the sexual behaviour of male Wistar rats. BMC Complement Altern Med 15:343
Gajbhiye SV, Jadhav KS, Marathe PA, Pawar DB (2015) Animal models of erectile dysfunction. India J Urol 31:15–21
Gan L, Hua Zhang S, Liang Yang X, Bi Xu H (2004) Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum. Int Immunopharmacol 4:563–569
Gao Y, Wei Y, Wang Y, Gao F, Chen Z (2017) Lycium barbarum: a traditional Chinese herb and a promising anti-aging agent. Aging Dis 8:778–791
Gooren L (1989) Androgens and estrogens in their negative feedback action in the hypothalamo-pituitary-testis axis: site of action and evidence of their interaction. J Steroid Biochem 33:757–761
Gross PM, Zhang X, Zhang R (2006) Wolfberry: Nature’s bounty of Nutrition & Health. Charleston: SC: Booksurge publishing
Hull EM, Lumley LA, Matuszewich L, Dominguez J, Moses J, Lorrain DS (1994) The roles of nitric oxide in sexual function of male rats. Neuropharmacology 33:1499–1504
Hull EM, Wood RI, McKenna KE (2006) The neurobiology of male sexual behavior in: Neill JD. and Pfaff DW (eds) The physiology of reproduction, Elsevier press: New York. In: pp 1729–1824
Jin M, Huang Q, Zhao K, Shang P (2013) Biological activities and potential health benefit effects of polysaccharides isolated from Lycium barbarum L. Int J Bio Mmacromol 54:16–23
Kleitz-Nelson HK, Dominguez JM, Cornil CA, Ball GF (2010) Is sexual motivational state linked to dopamine release in the medial preoptic area? Behav Neurosci 124:300–304
Kyratsas C, Dalla C, Anderzhanova E, Polissidis A, Kokras N, Konstantinides K, Papadopoulou-Daifoti Z (2013) Experimental evidence for sildenafil's action in the central nervous system: dopamine and serotonin changes in the medial preoptic area and nucleus accumbens during sexual arousal. J Sex Med 10:719–729
Lagoda G, Muschamp JW, Vigdorchik A, Hull EM (2004) A nitric oxide synthesis inhibitor in the medial preoptic area inhibits copulation and stimulus sensitization in male rats. Behav Neurosci 118:1317–1323
Lau BW, Lee JC, Li Y, Fung SM, Sang YH, Shen J, Chang RC, So KF (2012) Polysaccharides from wolfberry prevents corticosterone-induced inhibition of sexual behavior and increases neurogenesis. PLoS One 7:e33374
Li G, Sepkovic DW, Bradlow HL, Telang NT, Wong GY (2009) Lycium barbarum inhibits growth of estrogen receptor positive human breast cancer cells by favorably altering estradiol metabolism. Nutr Cancer 61:408–414
Li XM (2007) Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats. Int J Bio Mmacromol 40:461–465
Lin G, Li H, Zhang X, Wang J, Zaid U, Sanford MT, Tu V, Wu A, Wang L, Tian F, Kotanides H, Krishnan V, Wang G, Ning H, Banie L, Lin CS, Deng GG, Lue TF (2015) Novel therapeutic approach for neurogenic erectile dysfunction: effect of neurotrophic tyrosine kinase receptor type 1 monoclonal antibody. Euro Urol 67:716–726
Liu YC, Salamone JD, Sachs BD (1997) Impaired sexual response after lesions of the paraventricular nucleus of the hypothalamus in male rats. Behav Neurosci 111:1361–1367
Luo Q, Cui X, Yan J, Yang M, Liu J, Jiang Y, Li J, Zhou Y (2011) Antagonistic effects of Lycium barbarum polysaccharides on the impaired reproductive system of male rats induced by local subchronic exposure to 60Co-gamma irradiation. Phytother Res 25:694–701
Luo Q, Li Z, Huang X, Yan J, Zhang S, Cai YZ (2006) Lycium barbarum polysaccharides: protective effects against heat-induced damage of rat testes and H2O2-induced DNA damage in mouse testicular cells and beneficial effect on sexual behavior and reproductive function of hemicastrated rats. Life Sci 79:613–621
Mao F, Xiao B, Jiang Z, Zhao J, Huang X, Guo J (2011) Anticancer effect of Lycium barbarum polysaccharides on colon cancer cells involves G0/G1 phase arrest. Med Oncol 28:121–126
Marson L, Platt KB, McKenna KE (1993) Central nervous system innervation of the penis as revealed by the transneuronal transport of pseudorabies virus. Neuroscience 55:263–280
Melis MR, Succu S, Mauri A, Argiolas A (1998) Nitric oxide production is increased in the paraventricular nucleus of the hypothalamus of male rats during non-contact penile erections and copulation. Eur J Neurosci 10:1968–1974
Mungrue IN, Bredt DS, Stewart DJ, Husain M (2003) From molecules to mammals: what's NOS got to do with it? Acta Physiol Scand 179:123–135
Nutsch VL, Will RG, Hattori T, Tobiansky DJ, Dominguez JM (2014) Sexual experience influences mating-induced activity in nitric oxide synthase-containing neurons in the medial preoptic area. Neurosci Lett 579:92–96
Paxinos G, Watson C (1986).The rat brain in sterotaxic coordinates. Academic Press, Orlando
Pfaus JG (1999) Neurobiology of sexual behavior. Curr Opin Neurobiol 9:751–758
Portillo W, Unda N, Camacho FJ, Sanchez M, Corona R, Arzate DM, Diaz NF, Paredes RG (2012) Sexual activity increases the number of newborn cells in the accessory olfactory bulb of male rats. Front Neuroanat 6:25
Putnam SK, Sato S, Hull EM (2003) Effects of testosterone metabolites on copulation and medial preoptic dopamine release in castrated male rats. Horm Behav 44:419–426
Putnam SK, Sato S, Riolo JV, Hull EM (2005) Effects of testosterone metabolites on copulation, medial preoptic dopamine, and NOS-immunoreactivity in castrated male rats. Horm Behav 47:513–522
Reis M, Araujo LTF, de Andrade WMG, Resende NDS, Lima RRM, Nascimento ESD Jr, Costa M, Cavalcante JC (2018) Distribution of nitric oxide synthase in the rock cavy (Kerodon rupestris) brain I: the diencephalon. Brain Res 1685:60–78
Sachs BD (1995) Placing erection in context: the reflexogenic-psychogenic dichotomy reconsidered. Neurosci Biobehav Rev 19:211–224
Sachs BD (2000) Contextual approaches to the physiology and classification of erectile function, erectile dysfunction, and sexual arousal. Neurosci Biobehav Rev 24:541–560
Sachs BD, Akasofu K, Citron JH, Daniels SB, Natoli JH (1994) Noncontact stimulation from estrous females evokes penile erection in rats. Physiol Behav 55:1073–1079
Sato Y, Horita H, Kurohata T, Adachi H, Tsukamoto T (1998) Effect of the nitric oxide level in the medial preoptic area on male copulatory behavior in rats. Am J Physio 274:R243–R247
Shan X, Zhou J, Ma T, Chai Q (2011) Lycium barbarum polysaccharides reduce exercise-induced oxidative stress. Int J Mol Sci 12:1081–1088
Sohn DW, Kim HY, Kim SD, Lee EJ, Kim HS, Kim JK, Hwang SY, Cho YH, Kim SW (2008) Elevation of intracavernous pressure and NO-cGMP activity by a new herbal formula in penile tissues of spontaneous hypertensive male rats. J Ethnopharmacol 120:176–180
Suresh S, Prakash S (2011) Effect of Mucuna pruriens (Linn.) on oxidative stress-induced structural alteration of corpus cavernosum in streptozotocin-induced diabetic rat. J Sex Med 8:1943–1956
Vincent SR, Kimura H (1992) Histochemical mapping of nitric oxide synthase in the rat brain. Neurosci 46:755–784
Yakubu MT, Akanji MA, Oladiji AT (2005) Aphrodisiac potentials of the aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem in male albino rats. Asian J Androl 7:399–404
Yang M, Gao N, Zhao Y, Liu LX, Lu XJ (2011) Protective effect of Lycium barbarum polysaccharide on retinal ganglion cells in vitro. Int J Ophthalmol 4:377–379
Yeh KY, Wu CH, Tsai YF (2012) Noncontact erection is enhanced by Ginkgo biloba treatment in rats: role of neuronal NOS in the paraventricular nucleus and sacral spinal cord. Psychopharmacology 222:439–446
Zanoli P, Benelli A, Zavatti M, Rivasi M, Baraldi C, Baraldi M (2008) Improved sexual behavior in male rats treated with a Chinese herbal extract: hormonal and neuronal implications. Asian J Androl 10:937–945
Funding
This study was supported by a grant from the Ministry of Science and Technology (MOST 104-2410-H-241-001, MOST 105-2410-H-241-001, MOST-106-2410-H-241-002) of Taiwan.
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Huang, A.C., Wu, JM., Chang, YH. et al. Neuronal nitric oxide synthase activity mediates Lycium barbarum polysaccharides-enhanced sexual performance without stimulating noncontact erection in rats. Psychopharmacology 236, 1293–1301 (2019). https://doi.org/10.1007/s00213-018-5141-z
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DOI: https://doi.org/10.1007/s00213-018-5141-z