Sexual Function and The Brain

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What goes on in the brain before, during, and after sex?
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People engage in sexual activities for numerous reasons, mainly for pleasure or as a method of reproduction. Sexual function, which is defined by sexual desire, sexual arousal, and ejaculation or orgasm, is an important part of human nature. It is controlled by the endocrine system, neurotransmitter system, and central nervous system, all of which are involved in the excitation or inhibition of various neurochemical pathways or neuroanatomical structures [1]. Sexual desire is the craving for positive, sexual reinforcement through sexual activity, which leads to sexual arousal [2]; this state stimulates the enjoyment of sexual pleasure with the goal of ejaculation or orgasm [3]; ejaculation is the release of semen by males and orgasm is the discharge of sexual tension by males and females [4]. These conditions are excited or inhibited depending on the activity of various brain systems [1].

1.1 The Endocrine System on Sexual Function

The endocrine system encompasses many glands: the pineal gland, hypothalamus, pituitary gland, thyroid gland, parathyroid glands, thymus gland, adrenal glands, pancreas, and testes or ovaries. These glands maintain the body’s homeostasis by producing hormones and releasing them into the bloodstream to be transported throughout the body. The hormones regulate the body’s growth, metabolism, and sexual function; hormones that control the latter include oxytocin and prolactin [5].

1.1a Oxytocin

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Oxytocin, The Love Hormone
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Oxytocin is a neuropeptide hormone whose structure composes of a ring six amino acids long and tail three amino acids long. Its cell bodies are found in the paraventricular and supraoptic nuclei of the hypothalamus, and are projected to other regions at the posterior pituitary. Various sensory stimuli such as sexual thoughts, sexual smells, and breast and genital area stimulation release oxytocin.

Rat studies have shown that the administration of oxytocin into the paraventricular nuclei leads to erection in male rats and into the medial preoptic area or ventromedial hypothalamus leads to lordosis behavior in female rats. Oxytocin antagonist was shown to reduce lordosis behavior. Furthermore, oxytocin neurons are activated in the paraventricular nuclei in male rats when they associate specific aromas to positive sexual reinforcement behavior. Infusion of oxytocin allows for ejaculation and sexually conditioned partner preference in male rats, while oxytocin receptor antagonists prevent bonding. In addition, central or peripheral injection of oxytocin into the brains of male rats shortened the time from their first intromission to their first ejaculation, and from ejaculation to the next intromission. Injection of oxytocin into the brains of female rats increased their contact with male rats. Studies with other animals have also been conducted: In killifish, the administration of oxytocin was shown to cause spawning reflexes; in rabbits, it was shown to lead to a quick first ejaculation, and increase the number of ejaculations within the following, thirty-minute period [2] [6].

In humans, oxytocin levels increase during sexual arousal and orgasm. As oxytocin levels increase, the intensity of orgasmic contractions increases in males and females; this is also true in females who undergo multiple orgasms. In addition, as plasma oxytocin levels increase, positive mood and sexual interest increase. An artificial form of oxytocin, used to help with breast-feeding, was also shown to increase sexual desire and vaginal lubrication in females [1].

1.1b Prolactin

Prolactin is a neuropeptide hormone that is folded due to its three disulfide bonds. It is a heterogeneous molecule, thus it exists in many forms; there are three, mains forms: 1) little prolactin, which is a single polypeptide chain of 198 amino acids weighing 22kDa, 2) big prolactin, which weighs 48kDa, and 3) big, big prolactin, which weighs 150kDa. Prolactin is found in the anterior pituitary gland. It provides satisfaction after any sexual behavior [7].

In humans, high levels of prolactin decrease sexual desire; this can be fixed through the administration of dopamine agonists, which decrease prolactin levels. It has been shown that high amounts of prolactin increase anxiety and depression leading to a negative mood, which indirectly affects sexual function. Central or peripheral administration of prolactin into the brains of humans particularly affects their sexual arousal. It was found that prolactin levels increase one-and-a-half-folds after ejaculation in males and two-folds after orgasm in females; it remains at the increased state for the following, sixty minute period. The same is true for plasma prolactin levels. In females, the increase of prolactin after orgasm may be a result of neuroendocrine reflexes, which act to promote pregnancy; it is known that lactating females, who have high levels of prolactin, have decreased sexual desire and sexual arousal. Furthermore, extremely high amounts of prolactin lead to erectile dysfunction in males and amenorrhea and infertility in females [1] [8].

2.1 The Neurotransmitter System on Sexual Function

The neurotransmitter system is composed of a variety of neurotransmitters; the main classes are amino acids, peptides, and monoamines. They are packed into synaptic vesicles, which are released from the pre-synaptic membrane to the post-synaptic membrane via the synaptic cleft. Once they bind to the receptors on the post-synaptic membrane, action potentials occur and signals are sent throughout the body. These signals affect mood, sleep, and sexual function; neurotransmitters that affect the latter include dopamine and serotonin [9].

2.1a Dopamine

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Acute use of cocaine increases sexual function, but chronic use decreases it
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Dopamine is a monoamine neurotransmitter consisting of an amine group connected to a catechol structure. It has five receptors: D1, D2, D3, D4, and D5. Dopamine is produced in several areas of the brain, primarily the ventral tegmental area and substantia nigra. It plays a role in reward-seeking behavior [10].

Sexual desire and arousal is controlled by the mesolimbic, nigrostriatal, and hypothalamic dopamine systems in the brain. Mesolimbic cell bodies are found in the ventral tegmental area and are projected to various limbic and cortical structures, and nigrostriatal cell bodies are found in the substantia nigra and are projected to the striatum. Medications used to treat Parkinson’s disease are dopamine agonists, which increase sexual function. Administration of apomorphine causes erection in male rats and lordosis behavior in female rats, a behavior where the hip is raised to facilitate in intercourse; administration of L-DOPA increases libido in lazy, male rats. On the contrary, antipsychotic medications, such as trifluoperazine hydrochloride, which decrease dopamine activity, delay or inhibit erection or orgasm. It was shown that dopamine agonists increase copulation in sexually inactive, male rats, while dopamine antagonists decrease it in sexually active, male rats.

Both animals and humans showed increased motor activity when motivated by positive sexual reinforcement behavior. These behaviors include male guinea pigs running on the exercise wheels, male pigeons pecking keys, and male stickleback fish swimming through rings; primary reinforcers include ejaculation or orgasm and secondary reinforcers include facial expressions and smells. Dopamine agonists increase such behaviors, while dopamine antagonists decrease them. 

Steroid hormones increase the production and release of dopamine, which increases sexual function. For example, cocaine increases dopamine activity by blocking the pre-synaptic auto-receptors. However, prolonged use was shown to affect ejaculation in 30% of males and reduce sexual pleasure in 80% of females. Withdrawal from this drug temporarily reduced sexual desire, which was then brought back to normal levels within three weeks of abstinence. Therefore, acute administration of cocaine increases erection in males, while chronic administration decreases it [1] [2].

2.1b Serotonin

Serotonin is a monamine neurotransmitter made up of two rings. It consists of a hydroxyl group and two amine groups. It is found in the gastrointestinal tract, blood platelets, and central nervous system. Serotonin is known to affect erection or orgasm [11]. 

Psychoactive medications alter mood and behavior; they affect serotonin activity and play a role in sexual function. Serotonin neurons are found in the raphe nuclei in the midbrain and are projected throughout the body, even to the lumbar and sacral areas that control genital reflexes. Selective serotonin reuptake inhibitors (SSRIs) increase serotonin activity impairing orgasm in females, ejaculation in males, and libido in both; between 2% to 75% of humans taking SSRIs reported such side effects. It was shown that the activation of serotonin2 receptors decreases sexual function and serotonin1A receptors increases it. Nefazodone is an unusual SSRI, which leads to fewer side effects than the regular ones by decreasing its associations with serotonin2 receptors and increasing it with serotonin1A receptors. These side effects occur due to the actions exerted by serotonin in the periphery of the body; 95% of serotonin receptors are located there. For example, vasoconstriction occurs on the smooth muscles in the genital area activating sex organs.

Medications that cause serotonin to bind to post-synaptic receptors decrease sexual function, while those that inhibit serotonin from binding increase it. Serotonin agonists cause humans to have less gratification with sexual desire, sexual arousal, and erection or orgasm: the agonists lead them to feel guilty about masturbating, be less satisfied with their sexual partners, and have less intercourse. Administration of parachlorophenylalanine, an inhibitor of serotonin production, can be a used as a treatment for this [1] [2].

3.1 The Central Nervous System on Sexual Function

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The brain and spinal cord both play a major role in sexual function
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The central nervous system consists of the brain in the dorsal cavity and spinal cord in the cranial cavity. The brain has approximately one-hundred billion neurons; it can be divided into the forebrain, midbrain, and hindbrain. The spinal cord is enclosed by a vertebral column composed of bones. The central nervous system controls behavior by receiving and delivering information from and to all parts of the body. The brain is the most important sexual organ; hence impairments in brain areas such as the forebrain or brainstem can affect sexual function [12].

3.1a The Forebrain

The forebrain is a section of the brain consisting of the diencephalon and telencephalon; the former contains the thalamus and hypothalamus, while the latter contains the cerebrum. Together, they create the upper part of the brain. The forebrain is involved in sensory outputs, voluntary movement control, and higher processing functions; it also plays a role in sexual drive and pleasure [13].

The medial amygdala and the bed nucleus of the stria terminalis control sexual functioning in females; the former also controls sexual desire in males. In addition, stimulation of the hippocampus causes erection in males and septal region causes orgasms in females. Furthermore, when males were shown a sexually arousing picture, their right insula, right inferior frontal cortex, and left anterior cingulated cortex were activated [1].

3.1b The Brainstem

The brainstem is located in the posterior part of the brain, and connects the cerebrum with the spinal cord. It includes the medulla oblongata, pons, and midbrain. It allows motor and sensory neurons to travel through it passing signals from the brain to the spinal cord. The forebrain controls breathing, heart rate, and blood pressure; it is also involved in sexual arousal [14].

The nucleus paragigantocellularis, which projects into the pelvic efferent neurons and interneurons in the lumbosacral spinal cord, plays a role in orgasm in males and females. In addition, the raphe nuclei and locus ceruleus, which project to the lumbosacral spinal cord, play a role in sexual function. Moreover, lesions in the brainstem area inhibit sexual climax; this area also plays a role in the inhibition of ejaculation or orgasm caused by SSRIs [1].

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