Prenatal Hypoxia Ischemia Increases Male Rat Sexual Behavior.

INTRODUCTION: Research consistently indicates an association between prenatal hypoxia-ischemia (HI) and mortality and chronic neurological diseases in newborns. HI can cause permanent effects, including mental retardation, motor impairment, learning disabilities, epilepsy, and cerebral palsy. Moreover, little is known about the relationship between HI and sexual behavior. AIMS: The aims of this study are to examine whether HI is associated with changes in sexual behavior. METHODS: HI was induced by clamping the uterine arteries of pregnant rats. The arteries were clamped for 45 minutes on the 18th day of gestation (HI group). Shams received laparotomy and anesthesia only. Pups were born at term. At 90 days of age, sexual behavior was evaluated. Statistical analysis was performed using two-way analysis of variance and post hoc Bonferonni correction. MAIN OUTCOME MEASURES: The main outcome measures of sexual response were standard sexual behavior, homosexual behavior, and sexual attempt on nonreceptive females. RESULTS: The stimulatory effect of HI on male rat sexual behavior has been shown in various experimental models; these animals showed reduced mount, intromission and ejaculation latencies; increased copulatory efficiency; and homosexual mounting. Additionally, there was an increase in fighting in trying to mount an unreceptive female. CONCLUSION: Our results indicate that HI had a long-term effect on sexual behavior despite exhibiting motor skill impairment. Accordingly, injuries during the fetal period may cause behavioral problems in adulthood.

Defective nitric oxide-cyclic guanosine monophosphate signaling in patients with bipolar disorder: a potential role for platelet dysfunction.

OBJECTIVE: Bipolar disorder (BD) is associated with elevated cardiovascular mortality rates. We investigated the modulation of l-arginine-nitric oxide (NO) signaling in platelets from patients with BD at different phases. METHODS: Platelets obtained from 28 patients with BD and 10 healthy volunteers were analyzed for l-arginine transport, NO synthase (NOS) activity, cyclic guanosine monophosphate content, and biomarkers of oxidative stress. Expressions of NOS isoforms, soluble guanylyl cyclase, and arginase were also measured in platelets. Amino acid and C-reactive protein levels in plasma were assessed. RESULTS: Plasma concentrations of l-arginine (mean [M] ± standard error of the mean [SEM] = 97 ± 10 versus 121 ± 10 µM) and its transport into platelets (median [interquartile range] = 26.0 [28.6] versus 26.5 [43.9] pmol/10(9) cells per minute) did not differ between patients with BD and controls (p > .05). Patients with BD showed reduced NOS activity (M ± SEM = 0.037 ± 0.003 versus 0.135 ± 0.022 pmol/10(8) cells, p < .001), but not endothelial NOS, inducible NOS, and arginase expression, compared with controls (p > .05). Cyclic guanosine monophosphate content was reduced (M ± SEM = 0.022 ± 0.003 versus 0.086 ± 0.020 pmol/10(8) cells, p < .05) despite the absence of changes in soluble guanylyl cyclase expression (median [interquartile range] = 21.6 [15.5] versus 9.5 [9.4] arbitrary units, p > .05) in patients with BD. Superoxide dismutase activity, but not catalase activity, was increased in patients with BD in the manic phase (M ± SEM = 2094 ± 335 versus 172 ± 17 U/mg protein, p < .001). C-reactive protein was elevated only in manic episodes (M ± SEM = 0.8 ± 0.2 versus 0.1 ± 0.02 mg/L, p < .001). CONCLUSIONS: Impaired NO generation from platelets, inflammation, and oxidative stress may play pivotal roles in the multifaceted process of cardiovascular events in BD.

Sleep deprivation affects sexual behavior and tyrosine hydroxylase (TH) levels in sexually experienced male rats.

Paradoxical sleep deprivation (PSD) produces alterations in dopaminergic systems and also modifies sexual behavior. In this work we evaluated PSD effects on the sexual response and tyrosine hydroxylase (TH) expression in dopaminergic pathways related to sexual behavior of naive and sexual experienced rats. Male Wistar rats had their sexual behavior evaluated in 6 copulatory tests, with a 4 days interval. In these tests, the animals interacted with a receptive female and parameters that compose each component of the male sexual reply (initiation, arousal and ejaculation) were evaluated. After the 5th test, the animals were randomly divided in 2 groups, control and PSD, and 96 h later they were submitted to the last copulatory test. PSD facilitated the excitatory and the ejaculatory component, increasing the copulatory efficiency. In addition, reduced mount frequency and ejaculation latency were observed. The temporal patterning of the sexual behavior was modified, with reduction in the number of mount bouts. PSD per se was not able to modify TH levels, but in PSD sexual trained rats, an increase in the number of TH-immunoreactive cellular bodies in all dopaminergic areas evaluated was detected. Our data suggest that PSD facilitates the sexual response and this facilitation combined to sexual training could be the consequence of increased TH levels in dopaminergic pathways related to sexual reply.

The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior.

Ferraz MMD, Quintella SL, Parcial ALN, Ferraz MR. The effects of sildenafil citrate and L-NAME on male rat sexual behaviour. PHARMACOL BIOCHEM BEHAV. Erectile dysfunction (ED) affects up to 50% of men between 40 and 70years of age. Significant advances in the pharmacological treatment of ED occurred in recent years, most notably the introduction of the first oral selective phosphodiesterase type-5 inhibitor, sildenafil. This study investigated the effectiveness of chronic oral treatment with L-NAME in rats as an experimental model of erectile dysfunction to evaluate new pharmacological agents that affect the sexual response. The effects of chronic oral L-NAME treatment, separately or in combination with sildenafil, on the sexual behaviour of male rats were evaluated. Filtered water was used as a control. Acute administration of L-NAME did not alter the sexual response compared with control, but sildenafil administration facilitated sexual behaviour after acute and chronic administration. Chronic L-NAME treatment inhibited motivational and consummatory measures of male rat sexual behaviour. Sildenafil prevented the inhibitory effects of L-NAME. The present results confirm that chronic oral treatment with a nitric oxide synthase inhibitor may be a relevant peripheral ED model to evaluate the effects of drugs on erectile function of male rats.

Depression and cardiovascular disease: role of nitric oxide.

Both depression and cardiovascular disease are major public health problems. Growing evidence shows that depression is a risk factor for the development of coronary artery disease (CAD). However, the exact mechanisms underlying the interplay between depression and CAD remain to be elucidated. Depression adversely affects autonomic and hormonal homeostasis, resulting in metabolic abnormalities, inflammation, increased platelet aggregation and endothelial dysfunction. All of these pathological features lead to atherothrombosis and cardiovascular events. However, there is no clear evidence that anti-depressant drugs or psychotherapy will reduce the risk or improve the outcome of CAD. Recent studies suggest that the L-arginine-nitric oxide (NO) pathway is involved in the genesis of depression. NO has many physiological functions, including vasodilatation, neurotransmission and platelet aggregation inhibition. It is synthesised from the cationic amino acid L-arginine by a family of enzymes: NO synthases (NOS). There are three NOS isoforms: inducible NOS (iNOS), endothelial NOS and neuronal NOS (nNOS). The availability and transport of L-arginine modulate rates of NO biosynthesis in circulating blood cells and vasculature, which provides a protective effect against cardiovascular disease. In depressive patients, the L-arginine-nitric oxide pathway seems to be impaired. The present review seeks a better understanding of the mechanisms that could identify depression as a cardiovascular risk factor and introduce new possible therapeutic interventions.