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R Arletti

Publications and source records attributed to R Arletti.

At least 37 records · Page 2Linked to original sources

Aged rats are still responsive to the antidepressant and memory-improving effects of oxytocin.

Oxytocin, intraperitoneally injected to 26-month-old male rats 60 min before testing, significantly improved social memory (at doses of 3 and 6 ng/kg) and reduced the duration of immobility in the behavioral despair test (at doses of 50 and 500 micrograms/kg). These results are in agreement with previous data obtained in adult rats and indicate that aging does not compromise the social memory improving and antidepressant-like activities of oxytocin.

Aging↗

Polymodal dose-response curve for oxytocin in the social recognition test.

Available data concerning the effect of oxytocin on memory are often inconsistent. In the present study it was found that oxytocin, intracerebroventricularly injected to adult male rats in a dose range of 1 fg-10 ng/rat immediately after a 5-minute encounter with a juvenile, significantly reduces the social investigation time of the adult rat towards the same juvenile during a second encounter (120 min later) with two peaks of activity, at 10 fg and 1 ng/rat. Larger doses of oxytocin were ineffective. The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin, injected 5 min before oxytocin by the same route and at the same doses, while being ineffective per se, completely abolished the memory-improving effect of a low dose of oxytocin (1 ng/rat) and, on the other hand, turned into memory-improving the effect of a high dose of oxytocin (500 ng/rat).

Animals↗

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.

Animals↗

Old rats are unresponsive to the behavioral effects of adrenocorticotropin.

In 28 month-old male rats, the i.c.v. injection of adrenocorticotropin [ACTH-(1-24)] (4 micrograms/rat) did not induce the typical behavioral syndrome (excessive grooming, stretching, yawning, penile erections). This indicates that the behavioral effects of melanocortins are age-dependent, suggesting either an aging-linked impairment of the nervous circuitries involved or a reduction of the number (or affinity, or both) of the brain melanocortin receptors in the elderly.

Aging↗

Galantide stimulates sexual behaviour in male rats.

While intracerebroventricular injection of galanin (5 micrograms/rat) inhibited sexual behavior in experienced male rats--without producing any other locomotor or behavioral deficit-, injection of the galanin antagonist, galantide, by the same route (1 or 2 micrograms/rat) stimulated sexual behavior (improving arousal, motivation and performance indexes) and antagonized the effect of galanin. These data further suggest that galanin plays a physiological role in male sexual behavior.

Animals↗

Oxytocin enhances, and oxytocin antagonism decreases, sexual receptivity in intact female rats.

In intact, non-ovariectomized female rats in spontaneous behavioral estrus, the i.c.v. injection of oxytocin significantly increased lordosis quotient and lordosis duration, starting from a dose of 1 ng/rat. On the other hand, the oxytocin antagonist, d(CH2)5Tyr(Me)-[Orn]8-vasotocin, injected at the same doses and by the same route, decreased lordosis quotient and lordosis duration, and prevented the effect of oxytocin. These data further support the notion that oxytocin plays a physiological role in female sexual receptivity.

Animals↗

Benextramine, an NPY antagonist, improves sexual behavior in male rats.

In adult, sexually-experienced male rats, the NPY-antagonist benextramine--at the doses of 5 and 10 mg/kg i.p. and of 50 micrograms/rat i.c.v.--significantly and specifically improved several parameters of copulatory activity. These data may further support the idea that NPY plays a role in the complex regulation of male sexual function, seemingly at the brain level.

Animals↗

[Endogenous anti-analgesic systems].

Nociception is of vital importance for the organism, while its inhibition by endogenous opioid systems is usually a sign of surrender. Therefore, it must be assumed that endogenous analgesic systems are balanced, and in fact, under normal conditions, overwhelmed, by teleologically far more important anti-analgesic systems. The two main anti-analgesic systems--i.e., the melanotropinergic and the cholecystokininergic--are here reviewed for their role, not only in nociception, but in a wide variety of vital functions (endocrine, gastrointestinal, ingestive, reproductive, cardiovascular, immune, etc.). Available data strongly suggest that these systems (particularly the melanotropinergic one) play a key role in the overall homeostasis of the body. Moreover, modulation of endogenous anti-analgesic systems may disclose a new, unforeseen approach to the treatment of pain.

Analgesia↗

The effect of oxytocin on feeding, drinking, and male copulatory behavior is not diminished by neonatal monosodium glutamate.

The effect of oxytocin on feeding, drinking, and male copulatory behavior was studied in rats neonatally injected with monosodium glutamate (MSG), a treatment that destroys neuronal perikarya of the arcuate nucleus and depletes the brain of proopiomelanocortin-derived peptides (melanocortins, endorphins). Both oxytocin-induced inhibition of feeding (1 and 10 micrograms/rat ICV and 150 micrograms/rat IP) and drinking (75 and 150 micrograms/rat IP) and oxytocin-induced improvement of male copulatory behavior (200 ng/rat IP) were either unaffected or in fact increased by neonatal MSG treatment. These data suggest that oxytocin neither inhibits feeding and drinking nor improves male sexual behavior through the release of melanocortin peptide(s) in the brain.

Animals↗

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 microgram/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.

Animals↗

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.

Adolescent↗

Oxytocin-induced inhibition of feeding and drinking: no sexual dimorphism in rats.

The effect of oxytocin on feeding and drinking behaviours was compared in male and female rats. Dose-dependent feeding and drinking inhibition was observed in either sex to about the same degree, both following intracerebroventricular or intraperitoneal administration. The results were obtained whether in animals with free access to food and water or in schedule-fed animals fasting for 21h and in two different models of thirst (water deprivation for 16h, s.c. administration of hypertonic saline). These data show that there is no sexual dimorphism in oxytocin-induced inhibition of feeding and drinking.

Animals↗

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.

Aging↗

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 micrograms/rat) or intraperitoneally (IP) (375-3,000 micrograms/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(CH2)5Tyr(Me)-[Orn8]-vasotocin, ICV injected at the dose of 10 micrograms/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 micrograms/rat (ICV) or 93-750 micrograms/kg (IP). In the water deprivation model, ICV pretreatment with d(CH2)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.

Animals↗

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.

Animals↗

Influence of protease inhibitors on the antidepressant activity of oxytocin.

Both in the behavioral despair test and in the learned helplessness test, the antidepressant-like activity of oxytocin (0.500 mg/Kg i.p.) was prevented by the administration of a protease inhibitor (EACA, 400 mg/Kg i.p.; pepstatin, 0.1 mg/Kg i.p.). On the other hand, the linear tripeptide tail of oxytocin, MIF-1, was inactive in the behavioral despair test, and less active than oxytocin in the learned helplessness test. We conclude that the antidepressant activity of oxytocin is due to its cleavage to some smaller fragment(s) different from MIF-1.

Animals↗

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.

Animals↗