Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances

A continuously increasing amount of research shows that oxytocin is involved in numerous central functions. Among the functions in which oxytocin is thought to be involved are those that play a role in social and sexual behaviors, and the involvement of central oxytocin in erectile function and sexual behavior was indeed one of the first to be discovered in laboratory animals in the 1980s. The first part of this review summarizes the results of studies done in laboratory animals that support a facilitatory role of oxytocin in male and female sexual behavior and reveal mechanisms through which this ancient neuropeptide participates in concert with other neurotransmitters and neuropeptides in this complex function, which is fundamental for the species reproduction. The second part summarizes the results of studies done mainly with intranasal oxytocin in men and women with the aim to translate the results found in laboratory animals to humans. Unexpectedly, the results of these studies do not appear to confirm the facilitatory role of oxytocin found in male and female sexual behavior in animals, both in men and women. Possible explanations for the failure of oxytocin to improve sexual behavior in men and women and strategies to attempt to overcome this impasse are considered

Dopamine, erectile function and male sexual behavior from the past to the present: a review

Early and recent studies show that dopamine through its neuronal systems and receptor subtypes plays different roles in the control of male sexual behavior. These studies show that (i) themmesolimbic/mesocortical dopaminergic system plays a key role in the preparatory phase of sexual behavior, e.g., in sexual arousal, motivation and reward, whereas the nigrostriatal system controls the sensory-motor coordination necessary for copulation, (ii) the incertohypothalamic system is involved in the consummatory aspects of sexual behavior (penile erection and copulation), but evidence for its role in sexual motivation is also available, (iii) the pro-sexual effects of dopamine occur in concertnwith neural systems interconnecting the hypothalamus and preoptic area with the spinal cord, ventral tegmental area and other limbic brain areas and (iv) D2 and D4 receptors play a major role in the pro-sexual effects of dopamine. Despite some controversy, increases or decreases, respectively, of brain dopamine activity induced by drugs or that occur physiologically, usually improves or worsens, respectively, sexual activity. These findings suggest that an altered central dopaminergic tone plays a role in mental pathologies characterized by aberrant sexual behavior, and that pro-erectile D4 receptor agonists may be considered a new strategy for the treatment of erectile dysfunction in men

Dopamine, Noradrenaline and Differences in Sexual Behavior between Roman High and Low Avoidance Male Rats: A Microdialysis Study in the Medial Prefrontal Cortex

Roman High- (RHA) and Low-Avoidance (RLA) outbred rats, which differ for a respectively rapid vs. poor acquisition of the active avoidance response in the shuttle-box, display differences in sexual activity when put in the presence of a sexually receptive female rat. Indeed RHA rats show higher levels of sexual motivation and copulatory performance than RLA rats, which persist also after repeated sexual activity. These differences have been correlated to a higher tone of the mesolimbic dopaminergic system of RHA rats vs. RLA rats, revealed by the higher increase of dopamine found in the dialysate obtained from the nucleus accumbens of RHA than RLA rats during sexual activity. This work shows that extracellular dopamine and noradrenaline (NA) also, increase in the dialysate from the medial prefrontal cortex (mPFC) of male RHA and RLA rats put in the presence of an inaccessible female rat and more markedly during direct sexual interaction. Such increases in dopamine (and its main metabolite 3,4-dihydroxyphenylacetic acid, DOPAC) and NA were found in both sexually naïve and experienced animals, but they were higher: (i) in RHA than in RLA rats; and (ii) in sexually experienced RHA and RLA rats than in their naïve counterparts. Finally, the differences in dopamine and NA in the mPFC occurred concomitantly to those in sexual activity, as RHA rats displayed higher levels of sexual motivation and copulatory performance than RLA rats in both the sexually naïve and experienced conditions. These results suggest that a higher dopaminergic tone also occurs in the mPFC, together with an increased noradrenergic tone, which may be involved in the different copulatory patterns found in RHA and RLA rats, as suggested for the mesolimbic dopaminergic system

Ordinamenti portuali e territorio costiero di una comunità della Sardegna moderna: Terranova (Olbia) in Gallura nei secoli 15.-18.

Con la cessione del Regno di Sardegna ai Savoia, in seguito al trattato di Londra del 1718, si appalesa la vera situazione di quel Regno: dalla povertà di risorse, alle distruzioni provocate dalla guerre, dal malgoverno spagnolo, al fisco dissestato e all'esiguità delle rendite reali. Olbia che in passato era stata popolosissima e rigogliosa, si presenta scarsamente abitata, con uno scalo portuale in piena decadenza, «quasi senza riparazione di muraglia, havendo perso sino al nome di città, chiamandosi terra di Terranova» secondo la descrizione fornita ai funzionari del Regno sabaudo da un anonimo informatore

Involvement of nigral oxytocin in locomotor activity: a behavioral, immunohistochemical and lesion study in male rats

Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neuron

Biological activities and nutraceutical potentials of water extracts from different parts of Cynomorium coccineum L. (Maltese Mushroom)

Maltese Mushroom (Cynomorium coccineum L.) is a non-photosynthetic plant that has been used in traditional medicine for many centuries. In this paper, water extracts from the whole plant, external layer and peeled plant were studied to determine the main components responsible for its biological activities, i.e., its antimicrobial, antioxidant, and anti-tyrosinase activities; its cytotoxicity against mouse melanoma B16F10 cells; and its pro-erectile activity in adult male rats. The results of electron transfer and hydrogen transfer assays showed that the antioxidant activity was mainly due to anthocyanins in the external layer, whereas the external layer and peeled plant extracts both inhibited the microbial growth of several Gram-positive strains. In contrast, the whole plant extract had the highest anti-tyrosinase activity and exhibited pro-erectile activity when administered subcutane-ously. Overall, this study elucidated which parts of Maltese Mushroom are responsible for its antimicrobial, antioxidant, and anti-tyrosinase activities and thus which extracts have potential for use in nutraceutical formulation

Profiles of VGF peptides in the rat brain and their modulations after Phencyclidine treatment

From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia". We produced antibodies against different VGF peptides encompassing the N-terminus, but also C-terminus-, TLQP-, GGGE- peptide sequences, and the so named NERP-3 and -4. These antibodies were used to carry out specific ELISA and immunolocalization studies while mass spectrometry (MS) analysis was also performed to recognize the intact brain VGF fragments. We used a schizophrenia rat model, in which alterations in the prepulse inhibition (PPI) of the acoustic startle response occurred after PCP treatment. In normal rats, all the VGF peptides studied were distributed in the brain areas examined including hypothalamus, prefrontal cortex, hippocampus, accumbens and amygdaloid nuclei and also in the plasma. By liquid chromatography-high resolution mass, we identified different intact VGF peptide fragments, including those encompassing the N-terminus and the NERPs. PCP treatment caused behavioral changes that closely mimic schizophrenia, estimated by us as a disruption of PPI of the acoustic startle response. The PCP treatment also induced selective changes in the VGF peptide levels within certain brain areas. Indeed, an increase in VGF C-terminus and TLQP peptides was revealed in the prefrontal cortex (p < 0.01) where they were localized within parvoalbumin and tyrosine hydroxylase (TH) containing neurons, respectively. Conversely, in the nucleus accumbens, PCP treatment produced a down-regulation in the levels of VGF C-terminus-, N-terminus- and GGGE- peptides (p < 0.01), expressed in GABAergic- (C-terminus/GGGE) and somatostatin- (N-terminus) neurons. These results confirm that VGF peptides are widely distributed in the brain and modulated in specific areas involved in schizophreni

I ratti delle linee Roman (High e Low Avoidance) presentano differenze nel comportamento sessuale: ruolo del sistema dopaminergico mesolimbico

I RATTI DELLE LINEE ROMAN (HIGH E LOW AVOIDANCE) PRESENTANO DIFFERENZE NEL COMPORTAMENTO SESSUALE: RUOLO DEL SISTEMA DOPAMINERGICO MESOLIMBICO. Introduzione. I ratti delle linee Roman (RHA, High avoidance e RLA, Low avoidance) mostrano tratti comportamentali divergenti: i primi sono impulsivi e proni all’abuso di sostanze mentre i secondi sono iper-emotivi e proni a sviluppare sintomi depressivi. I ratti Roman differiscono anche nel comportamento sessuale: gli RHA, infatti, mostrano una maggiore motivazione e migliori prestazioni rispetto agli RLA. L’obiettivo di questo studio era indagare se queste differenze sono relate ad alterazioni nella funzione del sistema dopaminergico mesolimbico, che gioca un ruolo chiave nel comportamento motivato. Metodi. Sono stati misurati con la metodica della microdialisi intracerebrale i livelli di dopamina liberata nel nucleo accumbens di ratti RHA e RLA mai esposti prima a stimoli sessuali (naïve) oppure esperienti, quando esposti ad una femmina recettiva inaccessibile e durante la copula. Contemporaneamente, sono stati misurati diversi indici comportamentali motivazionali e di performance sessuale. L’analisi statistica è stata eseguita con ANOVA per disegni misti, seguita da test post hoc (P < 0.05). Risultati. Nei ratti RHA si riscontra una maggiore liberazione di dopamina nel nucleo accumbens rispetto ai ratti RLA sia in presenza di una femmina recettiva inaccessibile che durante l’interazione sessuale. Similmente a quanto osservato con i parametri comportamentali, le differenze sono maggiori tra i gruppi naïve, tendono a diminuire tra i gruppi esperienti, ma persistono anche dopo stabilizzazione del comportamento dovuta all’esperienza. Conclusioni. Le differenze di comportamento sessuale delle linee Roman possono essere dovute al differente tono funzionale del sistema dopaminergico mesolimbico, che nei ratti RLA appare più debole rispetto ai ratti RHA. Questa differente funzione del sistema dopaminergico mesolimbico può essere implicata anche nelle alterazioni presenti in altri aspetti del comportamento motivato di questi animali (ad es., assunzione di sostanze d’abuso, vulnerabilità alla depressione)

Neuroplastic changes in c-Fos, ΔFosB, BDNF, trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity

Sexual activity causes differential changes in the expression of markers of neural activation (c-Fos and Delta FosB) and neural plasticity (Arc and BDNF/trkB), as determined either by Western Blot (BDNF, trkB, Arc, and Delta FosB) or immunohistochemistry (BDNF, trkB, Arc, and c-Fos), in the hippocam pus of male Roman high (RHA) and low avoidance (RLA) rats, two psychogenetically selected rat lines that display marked differences in sexual behavior (RHA rats exhibit higher sexual motivation and better copulatory performance than RLA rats). Both methods showed (with some differences) that sexual activity modifies the expression levels of these markers in the hippocampus of Roman rats depending on: (i) the level of sexual experience, that is, changes were usually more evident in sexually naive than in experienced rats; (ii) the hippocampal partition, that is, BDNF and Arc increased in the dorsal but tended to decrease in the ventral hippocampus; (iii) the marker considered, that is, in sexually experienced animals BDNF, c-Fos, and Arc levels were similar to those of controls, while Delta FosB levels increased; and (iv) the rat line, that is, changes were usually larger in RHA than RLA rats. These findings resemble those of early studies in RHA and RLA rats showing that sexual activity influences the expression of these markers in the nucleus accumbens, medial prefrontal cortex, and ventral tegmental area, and show for the first time that also in the hippocampus sexual activity induces neural activation and plasticity, events that occur mainly during the first phase of the acquisition of sexual experience and depend on the genotypic/phenotypic characteristics of the animals

A Cluster of Three Single Nucleotide Polymorphisms in the 3′-Untranslated Region of Human Glycoprotein PC-1 Gene Stabilizes PC-1 mRNA and Is Associated With Increased PC-1 Protein Content and Insulin Resistance–Related Abnormalities

Glycoprotein PC-1 inhibits insulin signaling and, when overexpressed, plays a role in human insulin resistance. Mechanisms of PC-1 overexpression are unknown. We have identified a haplotype in the 3′-untranslated region of the PC-1 gene that may modulate PC-1 expression and confer an increased risk for insulin resistance. Individuals from Sicily, Italy, carrying the "P" haplotype (i.e., a cluster of three single nucleotide polymorphisms: G2897A, G2906C, and C2948T) were at higher risk (P &lt; 0.01) for insulin resistance and had higher (P &lt; 0.05) levels of plasma glucose and insulin during an oral glucose tolerance test and higher levels of cholesterol, HDL cholesterol, and systolic blood pressure. They also had higher (P &lt; 0.05–0.01) PC-1 protein content in both skeletal muscle and cultured skin fibroblasts. In CHO cells transfected with either P or wild-type cDNA, specific PC-1 mRNA half-life was increased for those transfected with P (t/2 = 3.73 ± 1.0 vs. 1.57 ± 0.2 h; P &lt; 0.01). In a population of different ethnicity (Gargano, East Coast Italy), patients with type 2 diabetes (the most likely clinical outcome of insulin resistance) had a higher P haplotype frequency than healthy control subjects (7.8 vs. 1.5%, P &lt; 0.01), thus replicating the association between the P allele and the insulin resistance–related abnormalities observed among Sicilians. In conclusion, we have identified a possible molecular mechanism for PC-1 overexpression that confers an increased risk for insulin resistance–related abnormalities