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Biomedical subjects

A Benelli

Publications and source records attributed to A Benelli.

At least 19 recordsLinked to original sources

Opposite effect of acute and subchronic treatments with Ferula hermonis on copulatory behavior of male rats.

Sexually potent and sluggish/impotent male rats were orally treated with an extract of Ferula hermonis (30 and 60 mg/kg). The acute administration stimulated sexual motivation in potent rats and improved copulatory performance in sluggish/impotent rats. This last effect was elicited only by the higher dose, which, in parallel, increased serum testosterone levels in rats. On the contrary, when the extract was subchronically administered (10 days) a marked reduction in the percentage of rats achieving ejaculation was detected, together with a general impairment of the copulatory pattern. Furthermore, the repeated administration of the extract (6 mg/kg/day for 10 days) resulted in a significant reduction of testosterone levels in comparison with controls. The present results discourage a repeated assumption of F. hermonis, while suggesting its acute administration to improve the performance in sexual dysfunctions.

Animals↗

Pharmacological manipulation of brain galaninergic system and sexual behavior in male mice.

RATIONALE: Available data suggest a complex role for the brain galaninergic system in male sexual behavior; however, the results so far obtained in animals with either galanin or galanin antagonists are conflicting. OBJECTIVE: To define the better influence of galanin on male sexual behavior by studying, in mice, (i) the effect of galanin and of the chimeric galanin peptide M40 on the copulatory performance, and (ii) galanin mRNA levels in hypothalamic arcuate and dorso-medial nuclei. METHODS: For the behavioral testing, only sexually sluggish male mice were used. Galanin mRNA levels were studied in both sexually potent and impotent mice by means of in situ hybridization. Standard behavioral parameters for sexual behavior were recorded or calculated. Synthetic galanin (0.05, 0.1 or 1 microg/mouse) and M40 (5 or 20 microg/mouse) were intracerebroventricularly (ICV) injected, 15 min before the copulatory test. Galanin mRNA levels were evaluated. RESULTS: In sexually sluggish male mice, both galanin (0.1 and 1 microg/mouse ICV) and M40 (20 microg/mouse ICV), significantly increased intromission frequency and ejaculation latency; M40 also improved copulatory efficacy. On the other hand, in the hypothalamic arcuate and dorso-medial nuclei, the levels of galanin mRNA were not significantly different in sexually potent and impotent male mice. CONCLUSIONS: These results show that in sexually sluggish male mice the ICV injection of either galanin or the chimeric analogue M40 greatly prolongs the duration of the copulation; without a reduction of the sexual drive or of the copulatory performance. On the other hand, the hybridization experiments seem to rule out an important physiological role of the brain galaninergic system in the regulation of male sexual behavior, at least in mice.

Animals↗

Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.

The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi.

Animals↗

Behavioral and developmental outcomes of prenatal and postnatal vanadium exposure in the rat.

The developmental and behavioral outcomes of uninterrupted exposure to vanadium was studied in the rat. Starting 3 days before birth and up to the 100th day of extrauterine life, rats received as drink either a water solution of vanadyl sulphate (300 mg l(-1)containing 70 mg l(-1)of vanadium element, which is equal to an ingested dose of about 10 mg kg(-1)per day of vanadium element) plus NaCl 5 g l(-1), or a water solution of NaCl 5 g l(-1), or plain water [up to weaning (25th day of extrauterine life) treatment was given to dams and offspring]. At weaning, survivors were fewer and body weight was found to be significantly lower in the offspring of vanadium plus NaCl-treated dams than in the offspring of the other two groups. After weaning, growth retardation continued to be significant in both vanadium plus NaCl- and NaCl-treated rats. Such an effect was more pronounced in males than in females. Locomotor activity--evaluated at 1 month of age--was not significantly different in the three groups of rats. In the open-field, male (but not female) vanadium plus NaCl-treated rats had a reduced outer ambulation, rearing posture and grooming activity, and an increased defecation, in comparison with the males of the NaCl group, and reduced rearing in comparison with control males. As concerns ingestive behaviors, the only significant datum was an increased water intake in NaCl-treated males. Finally, at the 100th day of life, working memory was significantly impaired in both vanadium plus NaCl- and NaCl-treated rats.

Animals↗

Influence of estrogens and oxytocin on germ cells death in the neonatal mammalian ovary.

During mammalian oogenesis, some processes involve proliferation and others drastic reduction of germ cells. This study reports on the role played by two hormones, estradiol monobenzoate and oxytocin, in the control of the number of germ cells in the neonatal mouse ovary. Female neonatal mice were treated with doses ranging between 0.1 and 1 microg/mouse of estradiol monobenzoate or oxytocin and sacrificed at 5 days of postnatal age. The results showed that in the animals treated with estrogen, follicular development was more advanced than that of controls. Further the number of germ cells in apoptosis was drastically reduced. In the animals treated with oxytocin, the follicular development was arrested at the stage of primary follicles. In addition, the number of apoptotic germ cells increased if compared with that of the controls.

Animals↗

L -sulpiride, at antidepressant dosage, prevents conditioned-fear stress-induced gastric lesions in rats.

It has been previously shown that long-term treatment with low doses of l-sulpiride is highly effective in rat models of depression and of anticipatory anxiety/panic behavior. The present study was aimed at investigating whether the same treatment can prevent the ulcerogenic effect of repeated inescapable stresses. In adult rats, the repeated (7 consecutive days) exposure to an uncontrollable stressful condition (inescapable 2.5 mA scrambled shock for 60 s) produced the development of gastric lesions (multiple punctiform telangiectasias in all rats, with superficial erosions or more severe ulcerations in 10 out 13 rats; score 4.67 +/- 0.44). l-sulpiride, intraperitoneally injected once a day at an antidepressant dose level (4 mg kg(-1) per day), starting 21 days before the beginning of the 7-day sequence of inescapable punishments ( = 28 daily treatments), almost completely prevented the stress-induced gastric injury (score 1.67 +/- 0.29; P< 0.001 vs saline-treated rats, Mann-Whitney U test). These results show that, in rats, a long-term treatment with low doses of l-sulpiride prevents the development of gastric lesions induced by chronic exposure to uncontrollable stress.

Animals↗

[In vitro study of periodontal ligament cells].

BACKGROUND: The aim of this research is to outline a procedure able to promote specific cellular differentiation and proliferation with consequent periodontal regeneration. To achieve this goal, use was made of various compounds supposed to have the capacity of aiding periodontal regeneration. METHODS: The cells utilised for this study were obtained from explants of human periodontal ligaments. Their proliferation and differentiation capacity was examined in the presence of: coral granules (350, 500 mu), collagene type 1, growth factors (Platelet derived growth factor, PDGF and Transforming growth factor beta 1, TGF beta 1), both on their own and in different combination with one another. The differentiation activity was evaluated by ultrastructural morphological method (Transmission electron microscope-TEM) and by spectrophotometric investigation of the alkaline phosphatasis (ALP). RESULTS: The data show that the coral granules and among the growth factors used only TGF beta 1 stimulate the differentiation activity of the periodontal ligament cells valued on the basis of their capacity of producing ALP. These data are supported by the observation with TEM. CONCLUSIONS: From these results it is suggested that there may be therapeutic efficiency in the periodontal field of substances promoting cellular proliferation and differentiation.

Cell Culture Techniques↗

Acute low doses of melatonin stimulate rat sex behavior: the role of serotonin neurotransmission.

Melatonin is known to inhibit male and female sex behavior, but this effect has been reported only after repeated administration of sustained doses of the hormone. The present experiments were performed in order to study the effects of acute treatment with low doses of melatonin on rat male and female sex behavior in a dose-response paradigm. After four mating tests with a receptive female, sexually active male rats of the Wistar strain were injected intraperitoneally (i.p.) with small doses of melatonin (10, 50 and 100 microg/kg) administered acutely 1 h before a 30-min mating test. Melatonin (50 and 100 ng/2 microl) or its analogs, 6-chloromelatonin (2 and 4 ng/2 microl) and 2-iodomelatonin (5 and 10 ng/2 microl) were also injected intracerebroventricularly (i.c.v.) 30 min before mating. Either treatments caused a reduction of the latency to the first mount, intromission and ejaculation. An increase in the frequency of mounts, intromissions and ejaculations was also observed. Inhibition of sexual activity was observed when a greater dose (1 mg/kg) of melatonin was repeatedly injected for 14 days. Female sex behavior, measured by the lordosis quotient in Wistar female rats, was not affected by acute treatment with the hormone, while it appeared to be inhibited by the repeated injection. The facilitating effect of acute i.p. or i.c.v. melatonin low doses on sexual activity of male rats was partially abolished by the pre-treatment with the non-selective melatonin antagonist, luzindole (0.25 mg/kg, injected subcutaneously), and totally suppressed by the injection of small quantities of serotonin or the 5H(2A)-5H(2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane into the amygdala. These results suggest that melatonin may exert opposite effects on male and female sex behavior depending on the dose and duration of treatment.

Amphetamines↗

Antitussive effect of K+ channel openers.

The effect of the K(ATP) channel openers, pinacidil and cromakalim, on coughing was studied in guinea pigs exposed to a nebulized aqueous solution of citric acid (0.50 M). Both pinacidil and cromakalim, subcutaneously administered 45 min before the test, inhibited coughing. The D50 (95% CI) were 0.95 +/- 0.90 mg/kg for cromakalim and 3.25 +/- 0.92 mg/kg for pinacidil. Under our experimental conditions, the D50 (95% CI) of codeine was 1.74 +/- 0.75 mg/kg. The combination of cromakalim and pinacidil with codeine produced an additive effect. An additive effect was also produced by the combination of pinacidil with the selective tachykinin NK2 receptor antagonist MEN 10,627 = [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2beta-5beta)]. The antitussive effect of pinacidil and cromakalim was not a consequence of a bronchodilating effect, which was absent at these dose levels under our experimental conditions. These results indicate that K(ATP) channel openers have an opioid-like antitussive effect and may suggest a novel approach to the symptomatic treatment of coughing.

Animals↗

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

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.

Animals↗

l-Sulpiride, at a low, non-neuroleptic dose, prevents conditioned fear stress-induced freezing behavior in rats.

Antidepressant drugs are effective in anxiety states, including panic disorder. Both clinical and animal studies indicate that l-sulpiride, at low, non-neuroleptic doses, has antidepressant activity. The present study examined the effect of an antidepressant dose of l-sulpiride (4 mg/kg per day SC), compared with a well-established antidepressant drug (fluoxetine, 3 mg/kg per day SC), in a rat model of anticipatory anxiety/panic behavior: conditioned fear stress-induced freezing behavior. Long-term (26 days) administration of l-sulpiride almost completely abolished freezing, a similar effect being produced by fluoxetine (freezing duration, in seconds: controls, 148.1 +/- 29.6; l-sulpiride, 27.5 +/- 8.3; fluoxetine, 72.0 +/- 15.2). The same doses of l-sulpiride (4 mg/kg SC) and fluoxetine (3 mg/kg SC) had no effect when administered for shorter periods (1, 5, or 12 days). No effect was produced by the long-term (26 days) administration of a neuroleptic dose of l-sulpiride (20 mg/kg per day SC). These results demonstrate that long-term administration of low, non-neuroleptic doses of l-sulpiride, is highly effective in an animal model of anticipatory anxiety/panic behavior.

Animals↗

Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats.

1. S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons in involved in the therapeutic mechanisms of antidepressants. 2. The effect of SAMe in an animal model of 'depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats. 3. Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg-1 daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg-1 daily i.p.) produced a similar effect after a 3 week treatment. 4. Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg-1 daily i.m.)--and in imipramine (10 mg kg-1 daily i.p.)--treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats. 5. Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test. 6. While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment. 7. These results show that SAMe reverses an experimental condition of 'depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects.

Animals↗

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

The penile erection-inducing effect of intracerebroventricularly (i.c.v.) injected adrenocorticotropin-(1-24) [ACTH-(1-24)] (4 or 10 microg/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.

Animals↗

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.

Animals↗

Galantide improves social memory in rats.

The role of galanin in memory paradigms has been largely evaluated. The galanin-antagonist galantide, a chimeric peptide obtained from amino acids 1-13 of galanin attached to the C-terminal fragment of bradykinin, has been found to improve social memory in 'social recognition' test when i.c.v. administered at doses varying from 6-6000 nmoles.

Animals↗

Effect of potassium channel modulators on male sexual behavior.

In the adult sexually experienced male rat, the intracerebroventricular (i.c.v.) injection of pinacidil, a KATP channel opener, at the dose of 100-150-300 micrograms/rat worsened the copulatory performance in the presence of a receptive female, whereas the administration of glibenclamide, a KATP channel blocker, at the dose of 0.5 and 3 mg/kg intraperitoneally (i.p.) had an improving effect. These data indicate that KATP channels in target neurons may play an important role in the physiology of male sexual behavior.

Animals↗

A new series of 6-chloro-2,3-dihydro-4(1H)-quinazolinone derivatives as antiemetic and gastrointestinal motility enhancing agents.

New 6-chloro-2,3-dihydro-4(1H)-quinazolinones (24-27) have been synthesized and evaluated for gastrointestinal prokinetic and antiemetic activities in comparison with structurally related benzamides (21-22) and 6-chloro-2,3-dihydro-(1H)-1,3-benzoxazolin-4-ones (28). Their key pharmacophoric element has been defined as a 6-membered ring replacing the "virtual ring" arising from the hydrogen bond between amidic nitrogen and methoxy group in metoclopramide (1) and structurally related benzamides (2-10). Variations of heterocycle linking groups have pointed out that a lipophilic aromatic group in position 1 plays an important role for pharmacological properties, while the steric restriction and the modification of the side-chain nucleophilicity are uneffective both for the in vitro and in vivo activity. Some of these compounds very effectively enhance gut peristaltic activity in vitro (rabbit jejunum), increase gastric emptying of a semisolid meal (in rats), and inhibit cisplatin-induced emesis (in pigeons), favourably comparing with cisapride.

Animals↗

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.

Animals↗