Rossana Arletti

Influence of oxytocin on feeding behavior in the rat

Oxytocin, whether administered intraperitoneally (IP) (375-6,000 micrograms/kg) or intracerebroventricularly (ICV) (1-10 micrograms/rat), dose-dependently reduced food consumption and time spent eating and increased the latency to the first meal in rats fasted for 21 hr. Pretreatment with the oxytocin antagonist d(CH2)5Tyr(Me)-[Orn8]vasotocin (ICV 10 micrograms/rat) completely prevented the feeding inhibitory effect of an equal dose of ICV oxytocin, and per se increased food intake. Our data further support the hypothesis that oxytocin plays the role of neurotransmitter or neuromodulator in the CNS, and suggest that its involvement in a number of homeostatic systems may include appetite control.

Oxytocin acts as an antidepressant in two animal models of depression

In the behavioral despair test in mice, oxytocin, i.p. injected 60 min before testing, significantly reduced the duration of immobility at doses of 0.250-1.0 mg/Kg; the effect being similar to that of imipramine (7.5-30 mg/Kg i.p.). A more powerful effect was obtained with a 10-day treatment schedule. In the learned helplessness test, oxytocin (0.500 mg/Kg/day i.p. for 8 days) significantly reduced the escape failures and the latency to escape, the effect being even more intense than that of imipramine (20 mg/Kg/day i.p. for 8 days). These results show a new behavioral effect of oxytocin, and further support its role of CNS regulatory peptide.

Oxytocin improves male copulatory performance in rats

The role of oxytocin in male copulatory performance was reexamined in rats. Adult male rats were trained seven times for copulatory behavior, at weekly intervals. Oxytocin, either intraperitoneally injected (200 ng/rat) or intracerebroventricularly infused (1 ng/rat in 4 microliter saline) 60 and 5 min, respectively, before the eighth test, significantly shortened both the ejaculation latency and the postejaculatory interval. The intracerebroventricular infusion of saline alone (4 microliter/rat) had no effect at all.

Nitric oxide is involved in male sexual behavior of rats

In male rats, whether sexually experienced or sexually naive, the intraperitoneal administration of L-arginine (the natural substrate for nitric oxide synthase) (10, 25, 50 mg/kg) both increased the percentage of copulating in sexually naive rats and improved the indexes of sexual performance in sexually experienced rats, whereas the intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME) (a potent inhibitor of nitric oxide synthase) (10, 25, 50 mg/kg) had opposite effects. In contrast, after intracerebroventricular administration, L-arginine (25, 50, 100 microg/rat) had no effect - whether in naive or in experienced rats - whereas L-NAME completely prevented ejaculation in naive rats, at the dose of 100 microg/rat, but had no effect at all in experienced rats, up to the dose of 300 microg/rat. Finally, a direct relationship seems to exist between male copulatory performance and nitric oxide synthase activity in a discrete and defined brain area, the paraventricular nucleus of the hypothalamus: indeed, nitric oxide synthase mRNA expression in this nucleus in sexually potent rats is about twice that in sexually impotent rats. It is concluded that nitric oxide synthase is involved in the expression of male sexual activity, in spite of some inconsistencies that are hard to interpret.

Stimulating property of Turnera diffusa and Pfaffia paniculata extracts on the sexual behavior of male rats

Abstract Sexually potent and sexually sluggish/impotent male rats were treated orally with different amounts of Turnera diffusa and Pfaffia paniculata fluid extracts (0.25, 0.50, 1.0 ml/kg). While having no effect on the copulatory behavior of sexually potent rats, both plant extracts – singly or in combination – improved the copulatory performance of sexually sluggish/impotent rats. The highest dose of either extract (1 ml/kg) (as well as the combination of 0.5 ml/kg of each extract) increased the percentage of rats achieving ejaculation and significantly reduced mount, intromission and ejaculation latencies, post-ejaculatory interval and intercopulatory interval. Neither extract affected locomotor activity. These results seem to support the folk reputation of Turnera diffusa and Pfaffia paniculata as sexual stimulants.

NGF is released into plasma during human pregnancy: an oxytocin-mediated response?

The presence of biologically active nerve growth factor (NGF) in the peripheral circulation of women during pregnancy, labour and lactation was investigated. Using a sensitive immunoenzymatic assay (ELISA), we found an approximately five-fold increase in plasma NGF levels during labour and lactation compared with the concentrations found at the term of gestation or in control healthy women. Since labour and lactation are characterized by activation of the hypothalamo-pituitary-adrenal axis and by high plasma levels of the neurohypophyseal hormone oxytocin, and since the intravenous injection of oxytocin in female rats causes a 176% increase in the hypothalamic levels of NGF, it is possible that the increased amount of circulating NGF is correlated with one or both of these events.

Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats

Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its effect on locomotion.

Sexual behavior of aging male rats is stimulated by oxytocin.

The effect of oxytocin on male sexual behavior was investigated in sexually normal or sexually sluggish 20-month-old rats. Rats were tested seven times, at weekly intervals, for copulatory behavior in the presence of receptive females. Oxytocin (0.1 microgram), injected intraperitoneally 60 min before the eighth test, significantly shortened the mount, intromission and ejaculation latencies and post-ejaculation intervals, the effect being proportionately greater in the sexually sluggish rats. These data confirm that oxytocin plays a facilitatory role in mating behavior and suggest that it may prove useful in conditions of copulatory inadequacy.

Sexual impotence is associated with a reduced production of oxytocin and with an increased production of opioid peptides in the paraventricular nucleus of male rats

Oxytocin plays a physiological stimulatory role on sexual behavior. Conversely, opioid neuropeptides play a physiological inhibitory role. Here we show that in sexually impotent rats there is a reduced expression of oxytocin mRNA and an increased expression of proenkephalin and pro-dynorphin mRNA in the paraventricular nucleus of hypothalamus (PVN), a brain structure of key importance for sexual behavior. These data suggest that an imbalance in the production of oxytocin and of opioid peptides in the PVN, with prevalence of opioid peptides, may underlie a condition of sexual impotence.

Nitric oxide is involved in the ACTH-induced behavioral syndrome

In many animal species, the ICV injection of ACTH and of several shorter sequences of the ACTH molecule (melanocortin peptides) induces a peculiar behavioral syndrome mainly characterized by excessive grooming and by repeated acts of stretching and yawning. In adult males, spontaneous penile erections with ejaculation are also induced. We have studied the effect of NO synthase inhibition on this behavioral syndrome. The IP injection of the NO synthase inhibitor L-NG-nitroarginine methyl ester (NAME) significantly prevented--at the doses of 50 and 100 mg/kg--all the behavioral symptoms induced by the ICV administration of ACTH(1-24) (4 micrograms/rat). On the other hand, the ICV injection of NAME (up to 300 micrograms/rat) had no influence on the ACTH-induced excessive grooming and stretching, while significantly inhibited the display of yawnings and penile erections. These data indicate that brain NO synthase is involved in the mechanism of ACTH-induced yawning and penile erections, whereas peripheral NO synthase is involved in the induction of stretching and grooming.