Biomedical subjects
Publications and source records attributed to A Benelli.
The effect of pinacidil and cromakalim, two KATP channel openers, on intestinal transit and castor oil-induced diarrhea was studied in mice. Both drugs, administered orally, dose dependently inhibited the intestinal propulsion of charcoal, and castor oil-induced diarrhea, comparing favorably with morphine. These results may suggest a new approach for the symptomatic treatment of diarrhea.
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.
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).
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.
The present study investigated the effect of allopregnanolone (5 alpha-pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.
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.
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.
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.
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.
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.
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.
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.
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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.
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.
The intraperitoneal injection of clenbuterol, a beta-2 adrenoceptor agonist which readily penetrates into the brain, modified the copulatory pattern of male rats. In sexually vigorous rats, the acute administration of clenbuterol at the dose of 0.1 or 1 mg/kg reduced the number of mounts and/or intromissions and increased the postejaculation interval, while the repeated administration (7 days) of a dose of 0.1 mg/kg/day had no effect. In sexually sluggish rats, both the acute (0.01 or 0.1 mg/kg) and repeated (0.1 mg/kg/day x 7 days) administration of clenbuterol increased the percent of animals achieving ejaculation and succeeding in initiating a new copulatory series within the respective cutoff times, and reduced mount, intromission and ejaculation latencies, as well as the postejaculation interval. These data show that clenbuterol negatively affects the copulatory behavior of sexually vigorous male rats, but improves that of sexually sluggish ones, and provide further evidence that central beta-receptor activation produces behavioral effects.
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.
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