Improved sexual behavior in male rats treated with a Chinese herbal extract: hormonal and neuronal implications

Aim: To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior ofadult male rats. Methods: The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely (onetime, 45 min before mating test) or subchronically (daily for 10 days) in sexually potent and sexually sluggish/impotentrats. Sexual behavior, serum levels of luteinizing hormone (LH) and testosterone (T) were evaluated in treatedrats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmissionwas assessed in the nucleus accumbens using a microdialysis technique. Results: In sexually potent rats, bothacute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromissionlatency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculationlatency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission andejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kgsignificantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylaceticacid levels in the nucleus accumbens, 30 min after the acute administration. Conclusion: The improvement in bothappetitive and consummatory components of sexual behavior observed in male rats treated with the extract could beascribed to increased serum T level in parallel with the activation of the central dopaminergic system

OXYTOCIN INHIBITS FOOD AND FLUID INTAKE IN RATS

Increasing evidence indirectly suggests a role for oxytocinergic neurons in the control of ingestive behaviors. The present study was aimed at directly investigating a possible effect of oxytocin on food and water intake in rats. Oxytocin, whether administered intracerebroventricularly (ICV) (1-10-mu-g/rat) or intraperitoneally (IP) (375-3,000-mu-g/kg) dose dependently inhibited food intake in freely feeding animals; in schedule-fed animals fasting for 21 h, oxytocin not only reduced food intake but also reduced the time spent eating and increased the latency to first meal. On the other hand, oxytocin antagonist d(CH-2)5Tyr(Me)-[Orn8]-vasotocin, ICV injected at the dose of 10-mu-g/rat, increased food intake and time spent eating and reduced the latency to first meal; moreover, it completely prevented the effect of oxytocin. Water intake was studied both in freely drinking animals and in three different models of thirst (water deprivation, hypertonic saline administration, angiotensin II injection). In all cases, oxytocin dose dependently inhibited water intake, in a dose range of 0.1-10-mu-g/rat (ICV) or 93-750-mu-g/kg (IP). In the water deprivation model, ICV pretreatment with d(CH-2)5Tyr(Me)-[Orn8]-vasotocin completely prevented the antidipsogenic effect of oxytocin. In conclusion, these data show that oxytocin directly inhibits food and water intake in rats, the effect being specifically mediated by brain oxytocin receptors. This may support the idea that the brain oxytocinergic system plays an important role in the regulation of ingestive behaviors

INFLUENCE OF OXYTOCIN ON NOCICEPTION AND MORPHINE ANTINOCICEPTION

In the hot plate test the intracerebroventricular (i.c.v.) injection of oxytocin produced a significant decrease in nociception, starting from the dose of 1 mug/rat. A comparable effect was obtained with 10-200 times higher intraperitoneal (i.p.) doses. The i.c.v. injection of the oxytocin antagonist d(CH2)5-Tyr(Me)-[Orn8]-vasotocin, while having no influence per se, completely prevented the antinociceptive effect of an equal i.c.v. dose of oxytocin. The antinociceptive effect of oxytocin was also prevented by naltrexone, and oxytocin caused a small but significant increase of the antinociceptive effect of morphine and of its duration. These data indicate that pharmacological amounts of oxytocin produce antinociception, that occurs through the activation of oxytocin receptors; endogenous opioid systems seem to be involved altogether

Influence of mirtazapine on the sexual behavior of male rats

Rationale. Impairment of sexual activity is one of the most frequent side effects of antidepressant drugs. The increase in the synaptic concentrations of serotonin seems to be mainly responsible. Mirtazapine is a novel antidepressant that increases the synaptic concentrations of both noradrenaline and serotonin; moreover, it is an antagonist at 5-HT2C receptors, whose activation is considered to be responsible for some typical effects of serotonin on the ejaculation process (retardation of ejaculation, anorgasmia).Objectives. To study the influence of mirtazapine on copulatory performance and sexual motivation in male rats, in comparison-or in combination-with fluoxetine. Methods. Copulatory performance was studied either in sexually experienced or in sexually naive rats; sexual motivation was studied in sexually experienced rats. Mirtazapine (1, 5 or 10 mg/kg), fluoxetine (10 mg/kg), and the combination of mirtazapine + fluoxetine (10+10 mg/kg) were subcutaneously (s.c.) administered either acutely or daily for 13 days. Results. After acute administration, mirtazapine decreased mount latency (ML) and intromission latency (IL), and increased mount frequency (MF) and ejaculation latency (EL). Fluoxetine had no significant effect on any of the sexual behavior parameters. After a 13-day treatment, mirtazapine increased ML, IL and MF; fluoxetine increased ML, IL and the intercopulatory interval (ICI); the addition of mirtazapine to fluoxetine produced a reduction of ICI and an increase of MF. Moreover, mirtazapine significantly improved the performance of rats in the sexual motivation test. Conclusions. The present results show that, on the whole, the acute administration of mirtazapine improves several parameters of the copulatory performance of male rats and strongly stimulates sexual motivation, while the repeated administration produces minor, conflicting effects. This effect of mirtazapine on male rat sexual behavior is to be ascribed to the antagonism at brain alpha(2) adrenergic auto- and hetero-receptors, with consequent increased release of noradrenaline and serotonin, and antagonism at 5-HT2C receptors, which are involved in the negative influence of serotonin on male sexual behavior

Diabetic rats are unresponsive to the penile erection-inducing effect of intracerebroventricularly injected adrenocorticotropin

The penile erection-inducing effect of intracerebroventricularly (i.c.v.) injected adrenocorticotropin-(1-24) [ACTH-(1-24)] (4 or 10 mu g/animal) was almost completely absent in diabetic rats, either 8 days or 2 months after streptozotocin administration. The other behavioral symptoms (stretching, yawning, excessive grooming) were unevenly affected: stretching was significantly reduced either in early or in long-standing diabetes; yawning was practically absent in early diabetes and significantly reduced at the highest dose of ACTH-(1-24) in long-standing diabetes; grooming was reduced only at the highest dose of ACTH-(1-24), both in early and in long-standing diabetes. The fact that ACTH-induced penile erections (a centrally mediated effect) are practically absent even a few days after streptozotocin injection suggests that diabetes mellitus-induced penile dysfunction occurs, at least in part, through central mechanisms, and is not solely the consequence of peripheral nerve and vascular lesions