ARTICLE INFO

Article Type

Original Research

Authors

Torkamani Noughabi   M. (1)
Vaezi   Gh.H. (*)
Abtahi Eivari   H. (2)
Hojati   V. (1)






(*) Biology Department, Science & Research Branch, Islamic Azad University, Tehran, Iran
(1) Biology Department, Damghan Branch, Islamic Azad University, Damghan, Iran
(2) Biochemistry Department, Medicine Faculty, Gonabad University of Medical Sciences, Gonabad, Iran

Correspondence


Article History

Received:  January  28, 2017
Accepted:  September 3, 2017
ePublished:  January 11, 2018

BRIEF TEXT


Yawning is a phylogenetic contagious behavior that can be seen in mammals, birds and reptiles, under different circumstances [1]. … [2-11]. Also, the penal erection is the ultimate result of smooth muscle relaxation in the penis, and this process is essentially a spinal cord reflex … [12].

Neuropharmacological studies show that yawning alone or with stretch and erection of the penis is under the control of neurotransmitters and various neuropeptides. Dopamine, acetylcholine, nitrogen oxide (NO), and peptides such as oxytocin and an adrenocorticotropic / α-melanocyte stimulating hormone have stimulating role while serotonin may act as stimulant or inhibitory [13, 14]. The serotonin (5-HT) has been suggested by Urba Holmgren et al. initially to be involved in the adjustment of the yawn [15]. Various studies have argued that the HT-5 probably plays a multiple roles in mediating yawn. 1- (3-Chlorophenyl) piperazine (m-CPP), agonist and mianserin, are antagonist of serotonin HT2C-5 receptors [16, 17].

Considering the various and multiple roles of serotonin compounds on yawn and penile erection, and considering the fact that the type of acute and chronic administration of agonist and antagonist of serotonin 5-HT2C receptor is important for these behaviors and their comparison, this study aimed to at determining the acute and chronic effects of the injection of chlorophenyl Piperazine and Mianserin on yawning and penile erection of adult male rats.

This study is experimental.

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30 wistar rats weighing 250-300 grams were used. Rats weighing 200 gram were prepared from the Razi Serum Center of Mashhad and transferred to the Animal Hospital of Gonabad University of Medical Sciences. They were then kept in cages for animals in groups of 3-4, and water and special foot (pellets) were kept in sufficient quantity for testing in order to reach the desired weight. The animals were kept in physical conditions with a 12-hour darkness-lightness period (7am-7pm), a temperature of 22±2°C, without any noise and noise pollution.

Rats were randomly divided into three groups of 10 including the group receiving saline subcutaneous injection as a control group, the group receiving subcutaneous injection of 1- (3-chlorophenyl) piperazine (Sigma, USA) at 0.5 mg / kg, and the group receiving the subcutaneous injection of Mianserin (Sigma, USA) at 0.2 mg. The volume of subcutaneous injection was 0.2 ml [18]. The tests were carried out from 9 to 13. After injection in the acute phase (first day) and chronic phase (fourteenth day), each rats were placed inside a box of Plexiglas measuring 30 × 30 × 30 cm and were observed and filmed for 60 minutes at 10-minute intervals , The number of yawns and the number of erections of the penis were measured. Infusion during 14 consecutive days was considered as a chronic phase. Yawning is defined by opening the mouth for 5 to 10 seconds, along with stretching movements and eye closure. The penile erection was recorded at the same time as a change in the state, stiffening and removal of the penis from the pod that was accompanied with genital cleanness and hip flexion [19]. Data were analyzed using PSS 13 software. The default assumption of the distribution of data was investigated by Kolmogorov-Smirnov test. One-way ANOVA and Tukey's post hoc test were used to compare the mean of the tested groups. Paired t-test was used to compare the variables within the groups.

Serotonin antagonist (Mianserin) in the acute phase showed a significant increase in the number of yawn in the 60 minutes period compared to the control group (p<0.01). Serotonin agonist (1- (3-chlorophenyl) piperazine) showed a significant decrease in the number of yawning in the acute phase compared to the mianserin (p <0.01). In comparing acute and chronic groups, the chronic group of Mianserin showed a significant reduction in the number of yawning compared to the acute group (p<0.05). Chronic chlorphenyl piperazine group showed a significant increase compared to the acute group in the number of yawns (p<0.05; Figure 1).In the acute phase, mianesrin showed significant increase in the number of penile erection in 60 minutes compared to the control group (p<0.05). Chlorophenyl piperazine also showed a significant decrease in number of penile erection in the acute phase compared to the mianserin (p<0.01). Compared to acute and chronic groups, the chronic group of miaserin showed a significant decrease compared to the acute group in the penile erection (p<0.05). Chlorophenyl piperazine increased the number of erection in the penis in the chronic phase, but this increase was not significant (p>0.05; Figure 2).

Previous studies have shown that an increase in dose-dependent yawning has been observed following systemic administration of the HT2c serotonin-5 agonist, such as m-CPP, and injection of m-CPP and trifluoromethyl phenyl piperazine (T-FMPP) when injected into the parontotrichular nucleus (PVN), is not contrary to apomorphine and oxytocin which induce yawning and erection of the penis, and shows that the serotonergic upward path from the nucleus of the rheum to the PVN nucleus, which expresses the induction, is not involved in m-CPP and T-FMPP responses [15, 16]. The study showed that m-CPP reduced yawning and penile erection, and miaserin had an adverse effects as it increased yawning and erection of the penis. Probably, different serotonin receptors can have a different effect on yawning and different behaviors. These findings indicate that yawning and penile erection can be adjusted differently in different experimental and drug conditions. Serotonergic neurons (5-HT) play a role in controlling the sexual behavior of humans and animals, and 5-HT routes have an inhibitory effect on male sexual behavior [20]. However, these pathways may have inhibitory effects on the receptor, in different regions of the nervous system. Also, the effects may vary in different species [21]. Nerve endings have 5-HT neurons across the central nervous system and 5-HT neuronal cells can be seen in the central core of the rheophyte and the abdominal lattice, including paragigantocellularis, as well as the lumbosacral region of the spinal cord in relation to somatic and autonomic output to the pelvis [21]. Reducing the amount of 5-HT is usually accompanied by increased inhibition of serotonin synthesis (para-chlorophenylalanine), degradation of axons containing 5 and 7-dihydroxytryptamine, or electrolyte degeneration of the back of the rheophyte with increasing sexual activity [22]. The dominant 5-HT role in mediation of the central nervous system of the operation of penile erection is associated with inhibitory control of spinal cord reflexes including brain reflexes [21]. … [23]. Previous studies using the immunohistochemistry method have shown that superior spinal cord serotonergic erection control of the lumbosacral surface is strongly associated with the activation of 5-HT2C receptors. m-cpp and TFMPP act as partial agonists for 5-HT2C receptors and are usually antagonistic to 5-HT2A receptors. Both medications inhibit sexual behavior. RSD992, the receptor agonist of HT2C5, stimulates erection and male sexual behavior [24]. In this study, according to previous studies m-CPP, an inhibitory effect on the number of penile erections in acute phase showed that 5-HT2C receptor plays an important role in erectile control. Agonists may increase or decrease sexual function, and this depends on the type of receptor stimulated. Earlier studies have shown that increasing NO leads to yawning [16] and penile erection [13].

It is suggested that the different prescribing methods for 1- (3-chlorophenyl) piperazine and interperitoneal in acute and chronic phases and their effect on yawning and penile erection be considered.

The limitations of this study include the lack of facilities for injection of desired compounds into different brain regions, such as Stereotactic region.

Acute and chronic administrations of mianserin, respectively, increase and decrease the number of yawning and penile erection in rats. 1- (3-chlorophenyl) piperazine increases the number of yawns only in the chronic phase.

Azad University of Damghan and Gonabad University of Medical Sciences are thanked and appreciated.

Non-declared

All stages of the trial were performed according to the approved protocol of the ethics committee of Islamic Azad University, Damghan Branch. Observance of animal rights in laboratory for research on human use is based on the international guidelines for the care and use of laboratory animals

The cost of implementing this research project has been provided by Mehdi Turkmeni, a Ph.D. student of physiology at Islamic Azad University, Damghan branch.

TABLES and CHARTS

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CITIATION LINKS

[1]Argiolas A, Melis MR. The neuropharmacology of yawning. Eur J Pharmacol. 1998;343(1):1-16.
[2]Barbizet J. Yawning. J Neurol Neurosurg Psychiatry. 1958;21(3):203-9.
[3]Graves FC, Wallen K. Androgen-induced yawning in rhesus monkey females is reversed with a nonsteroidal anti-androgen. Horm Behav. 2006;49(2):233-6.
[4]Baenninger R. On yawning and its functions. Psychon Bull Rev. 1997;4(2):198-207.
[5]Laskiewicz A. Yawning with regard to the respiratory organs and the ear. Acta Oto Laryngologica. 1953;43(2-3):267-70.
[6]Provine RR, Tate BC, Geldmacher LL. Yawning: No effect of 3-5% CO2, 100% O2, and exercise. Behav Neural Biol. 1987;48(3):382-93.
[7]Gallup AC, Gallup GG JR. Yawning and thermoregulation. Physiol Behav. 2008;95(1-2):10-6.
[8]Elo H. Yawning and thermoregulation. Sleep Breath. 2010;14(4):391-2.
[9]Elo H. Yawning cannot cause significant temperature decreases in humans. Sleep Med. 2011;12(1):102-6.
[10]Guggisberg AG, Mathis J, Hermann US, Hess CW. The functional relationship between yawning and vigilance. Behav Brain Res. 2007;179(1):159-66.
[11]Campbell MW. de Waal FB. Ingroup–outgroup bias in contagious yawning by chimpanzees support link to empathy. PLoS ONE. 2011;6(4):e18283.
[12]Andersson KE . Pharmacology of penile erection. Pharmacol Rev. 2001;53(3):714-50.
[13]Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63(4):811-59.
[14]Walusinski O. The mystery of yawning in physiology and disease, foreward. Front Neurol Neurosci. 2010;28:X-XIV.
[15]Urba Holmgren R, Holmgren B, Rodriguez R, Gonzalez RM. Serotonergic modulation of yawning. Pharmacol Biochem Behav. 1979;11(3):371-2.
[16]Melis MR, Stancampiano R, Argiolas A. Role of nitric oxide in penile erection and yawning induced by 5-HT1c receptor agonists in male rats. Naunyn Schmiedebergs Arch Pharmacol. 1995;351(4):439-45.
[17]Berendsen HH, Jenck F, Broekkamp CL. Involvement of 5-HT1C-receptors in drug-induced penile erections in rats. Psychopharmacology (Berl). 1990;101(1):57-61.
[18]Sanna F, Melis MR, Angioni L, Argiolas A. Clavulanic acid induces penile erection and yawning in male rats: Comparison with apomorphine. Pharmacol Biochem Behav.2013;103(4):750-5.
[19]Torkamani Noughabi M, Vaezi Gh, Abtahi Hand Hojati V. Acute and chronic effects of opiates and dopamine on yawning, penile erection and genital grooming behaviors in male Wistar rats. Biomed Res. 2017;28(16):69316. [Persian]
[20]Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: Influences on male sexual behavior. Physiol Behav. 2004;83(2):291-307.
[21]Paredes RG, Contreras JL, Agmo A. Serotonin and sexual behavior in the male rabbit. J Neural Transm (Vienna). 2000;107(7):767-77.
[22]Kondo Y, Yamanouchi K, Arai Y. P-chlorophenylalanine facilitates copulatory behavior in septal lesioned but not in preoptic lesioned male rats. J Neuroendocrinol. 1993;5(6):629-33.
[23]Ridet JL, Tamir H, Privat A. Direct immunocytochemical localization of 5-hydroxytryptamine receptors in the adult rat spinal cord: A light and electron microscopic study using an anti-idiotypic antiserum. J Neurosci Res. 1994;38(1):109-21.
[24]Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38(8):1083-152.