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Biomedical subjects

D Giuliani

Publications and source records attributed to D Giuliani.

At least 37 records · Page 2Linked to original sources

Differential behavioral response to dopamine D2 agonists by sexually naive, sexually active, and sexually inactive male rats.

This study was performed with male rats categorized as sexually naive (SN), sexually active (SA), or sexually inactive (SI). In a first experiment the effects of dopamine (DA) D2 agonist SND 919 (0.05, 1, and 10 mg/kg) on the copulatory behavior of SN, SA and SI rats were assessed. In a second experiment the DA D2 agonist B-HT 920 (0.2 mg/kg) was used, and examination was limited to SN and SA rats. The effects exerted on stretching-yawning, penile erection, and sedation by the same compounds at the same doses in these three rat categories were also investigated. The main findings were that SND 919 and B-HT 920 facilitated ejaculation in SA rats, and that the rats that were different as regards level of sexual activity exhibited different behavioral responses to the two DA agonists.

Animals↗

Antioxidant effects of vitamin C in mice following X-irradiation.

The influence of supplemental vitamin C on the survival of nucleated bone marrow cells was examined in Swiss Webster mice following whole-body sublethal X irradiation (3.5 Gy). The vitamin protected these cells by a factor of 1.7 when cell count per tibia was taken as the biological end point. However, in studies with lethal whole-body irradiation (9 Gy) and 30 day survival as the end point, supplemental ascorbic acid (AA) had no significant effect on the biological outcome. Based on these studies, it appears that vitamin C is effective in protecting the nucleated cells at lower doses, but not at lethal doses. Studies on the mechanism of radioprotection by vitamin C at sublethal doses were carried out by following the response of endogenous AA and glutathione levels to X irradiation (3.5 Gy) on mice fed with regular as well as vitamin C rich diet. The results suggest that i) a glutathione controlled feedback mechanism regulates the plasma AA levels in mice; ii) the role of vitamin C against radiation damage is not only in the initial stages of radical scavenging but also in cellular redox processes mediated by glutathione.

Animals↗

Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919.

Behavioral differences towards receptive females, involving latency to the first contact, amicable behavior, genital exploration, and copulatory pattern, were seen in sexually active (A), sluggish (S), and inactive (I) male rats classified on the basis of 11 consecutive mating tests. The D2 dopamine agonist SND 919 (1 mg/kg) was intraperitoneally administered to the three groups 25 min before a 12th test; the drug stimulated the copulatory behavior of A and S but not of I rats in which it diminished genital exploration and amicable behavior. In a 13th test, conducted 1 week later, 31% of I initiated mating, 16% of them reaching ejaculation. The stimulant effect of SND 919 on copulation in A rats was confirmed in further experiments where it was injected at 0.1 mg/kg, a dose selective for the D2 autoreceptors.

Animals↗

Behavioural assessment in rats of the antipsychotic potential of the potent dopamine D2 receptor antagonist, (-)eticlopride.

The effects of the selective D2 DA receptor antagonist, (-)eticlopride, a drug belonging to the benzamide class, were investigated on the D2 DA agonist SND 919- and CQP 201-403-induced stereotyped behaviour and on CQP 201-403-induced shaking, in rats, and on isolation-induced aggression, in mice. (-)Eticlopride was also tested over a wide dose range (5-1200 micrograms kg-1, s.c.) for sedative and cataleptic activity, in rats. For comparison, some experiments were performed with (-)sulpiride (10 and 40 mg kg-1, s.c.) The data obtained show that (-)eticlopride differs from (-)sulpiride and potentially modifies animal behaviour, whether spontaneous or induced; moreover, they suggest a potential clinical use for this neuroleptic in the management of psychotic states.

Aggression↗

Macular blood flow velocity in sickle cell disease: relation to red cell density.

AIMS/BACKGROUND: While the retinal lesions of sickle cell retinopathy have been well documented, their pathogenesis remains unclear. The purpose of this study was (1) to compare macular blood flow velocity in patients with sickle cell disease and controls, and (2) to determine in sickle cell patients the relation between macular blood flow velocity and red blood cell density. METHODS: Macular blood flow velocity was measured in 18 patients with stable sickle cell disease and 45 normal controls using blue field entoptoscopy. Red blood cell density was determined by the phthalate ester density method. RESULTS: There were no significant differences between patients and controls for leucocyte velocity. However, in the sickle cell patients leucocyte velocity in the macular capillaries was significantly negatively associated with greater range of red blood cell density (p < 0.002 and p < 0.04 for right and left eyes, respectively). CONCLUSION: These results suggest that in sickle cell patients heterogeneity of the density of the red blood cells may slow down macular capillary blood flow.

Adult↗

The effect of human cord blood on SJL/J mice after chemoablation and irradiation and its possible clinical significance.

There is evidence from the existing published literature that human umbilical cord blood, when used for purposes of bone marrow transplantation, does not necessarily have to be HLA matched in order to be efficacious. These reports include experimental observations on the ability of human umbilical cord blood to rescue lethally irradiated mice and clinical observations from China wherein HLA mismatched umbilical cord blood has been engrafted successfully in children with malignant disease. The study reported herein describes an experimental immunocompetent murine model to determine if human umbilical cord blood can be used to improve survival after chemoablation and irradiation. The animals received chemoablation followed by irradiation, and irradiation alone. The presence of human DNA in these mice following injection of human umbilical cord blood cells was determined, and the immunological status of the animals was evaluated. Animals receiving human umbilical cord blood cells after chemoablation and irradiation had a better mean survival at day 50 than animals receiving syngeneic marrow. Human DNA could be found in various organs, particularly the lung, spleen and liver of the mice for the first 30 days. Thereafter, human DNA became more difficult to detect but trace amounts of human DNA could be found up to one year later. The results of mixed lymphocyte reactions and phenotype analyses for murine T cell markers performed after injection of HUCB cells both indicated endogenous repopulation, and relatively intact immune systems in these mice. Since human umbilical cord blood allowed mice to survive the lethal effects of chemoablation plus irradiation, or irradiation alone, with reconstitution of the animals' own, relatively intact, immune systems, it would appear that HLA mismatched human umbilical cord blood could potentially be used as an adjuvant treatment for patients with advanced malignancies or other diseases for which hematopoietic reconstitution is indicated.

Animals↗

The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat.

The selective D2 antagonist eticlopride, at a dose (0.01 mg/kg, s.c.) that fails to modify the normal behavior of rats, significantly reversed all the behavioral effects exerted by the selective D2 agonist SND 919 (0.1 mg/kg, i.p.), namely, the stimulation of stretching-yawning, penile erection and sedation and the inhibition of grooming. In the copulatory test, eticlopride at the same dose did not affect animal sexual behavior but potently counteracted the reduction in mount and intromission frequency and latency to ejaculation induced by SND 919 at 0.1 mg/kg, a behavioral pattern which might possibly be proposed as an animal model for human ejaculatio praecox.

Animals↗

Effect on rat feeding behavior of two selective D2 dopamine agonists.

B-HT 958 and SND 919, two selective agonists at D2 dopamine receptors, were examined for their influence on the feeding behavior of fasted rats. When food intake was determined in the rat's individual home cage, it was found to be reduced by both drugs at low sedative doses during the first hour after treatment and by SND 919 at the highest dose (which also elicits stereotypy) only 24 h later. However, SND 919 and B-HT 958 had no significant effect on feeding evaluated according to the X-maze and tube feeding tests. Analysis of the results, seen in the context of other behavioral signs produced by the drugs, suggests that data on feeding may vary depending on the experimental model used and can be modified by extraneous factors that interfere with a specific effect on food intake.

Adrenergic alpha-Agonists↗

Influence of idazoxan on the dopamine D2 receptor agonist-induced behavioural effects in rats.

The behavioural effects in rats of the dopamine D2 receptor agonists, lisuride, B-HT 920 and SND 919, were variously influenced by pre-treatment with the selective alpha 2-adrenoceptor antagonist, idazoxan (2 mg/kg), depending on the nature of the effect in question and the doses of agonist employed. The influence of idazoxan on drug-induced stretching-yawning, penile erection, sedation, stereotyped behaviour, aggressiveness and mounting is described and tentatively interpreted in neurochemical terms, account being taken of the activity of respective alpha 2-adrenoceptor antagonist and dopamine receptor agonists used, at alpha 2-adrenoceptors and at different dopamine D2 receptor subtypes, pre- and postsynaptically located.

Adrenergic alpha-Antagonists↗

Behavioural evidence that different neurochemical mechanisms underly stretching-yawning and penile erection induced in male rats by SND 919, a new selective D2 dopamine receptor agonist.

The behavioural effects induced in male Wistar rats by SND 919, a new drug reputed to have selective agonistic activity at D2 dopamine (DA) receptors, were studied. The following aspects of behaviour were considered: motor activity, stretching-yawning (SY), penile erection (PE) and stereotyped behaviour (SB). Intraperitoneal injection (IP) of the drug (0.01-20 mg/kg) induced an SY syndrome in the form of a bell-shaped dose-response curve, the effect being maximal at the dose of 0.1 mg/kg and disappearing completely at 10 mg/kg. SND 919 also potently elicited PE; this latter effect, however, was not coincident with SY induction, being maximal at 1 mg/kg and persisting at 10 and 20 mg/kg. SND 919-induced SY was potently antagonized by pretreatment not only with the D2 antagonist, L-sulpiride (20 mg/kg), but also with the alpha 2 antagonist, yohimbine (1, 3 mg/kg), and the more selective alpha 2 antagonist, idazoxan (1, 2 and 5 mg/kg). While sulpiride also decreased SND 919-induced PE, idazoxan at all doses and yohimbine at 1 mg/kg did not affect this behaviour. Inhibition of motor activity was induced by the D2 agonist at low doses (0.05, 0.1 mg/kg), while at high doses (1, 10 and 20 mg/kg), it was actually replaced by a form of SB characterized by downward sniffing and licking. When, for comparison, the D2 agonist, RU 24213 (0.1-20 mg/kg IP), was tested for PE, SY, motor activity and SB, it displayed a behavioural pattern very similar to that obtained with SND 919. Idazoxan (2 mg/kg), administered before RU 24213 (10 mg/kg), significantly antagonized the drug-induced SY, but not PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Behavioural effects induced in rats and chicks by D2 dopamine agonists.

In a first series of experiments, different selective dopamine D2 receptor agonists (B-HT 920, B-HT 958, SND 919, CQ 32-084, CQP 201-403, and lisuride) and the D1/D2 agonist apomorphine were IP injected into adult male rats. At low doses, they elicited repeated episodes of penile erection and stretching-yawning: at all doses tested, B-HT 920, B-HT 958, and CQ 32-084 also induced hypomotility, a sign that, in the case of high doses of SND 919, CQP 201-403, lisuride, and apomorphine, was replaced by stereotyped behaviour. In a second series of experiments, the same D2 agonists and the mixed D1/D2 agonist apomorphine were IP injected at the same doses into chicks. The following behavioural signs were observed: hypomotility, sleep-like state, and stereotyped pecking. The results show that: 1. there are similarities between the behavioural effects induced by the DA agonists in rats and chicks; and 2. in both species some behavioural signs elicited by the DA ergic compounds are useful pointers to their specific neurochemical activity.

Animals↗

Behavioural profile in the chicken of CQ 32-084 and CQP 201-403, two dopamine agonists.

CQ 32-084 and CQP 201-403, two ergot derivatives that previous behavioural studies in rats had suggested to be differently active on dopamine (DA) receptors, were IP injected into male chickens. Both compounds strongly modified the animals' behaviour. CQ 32-084 led to sedation, increased yawning, and decreased preening, while CQP 201-403 exerted a biphasic activity: At a low dose, it elicited sedation and yawning; at high doses, however, it induced a state of excitation manifested by diminished sedation and yawning, enhanced preening, and pecking. The sedation, increased yawning, and decreased preening induced by the two DA agonists were reversed by the D2-selective antagonist, sulpiride. The present studies indicate that, from a behavioural point of view, chickens respond similarly to rats to the DA agonists CQ 32-084 and CQP 201-403, which differ in their selectivity of action on the various DA receptor subtypes.

Animals↗

Suppressive effect of the dopamine D2 receptor agonist B-HT 920 on rat grooming.

The effect of the D2 agonist B-HT 920 was examined on three behavioural models of induced grooming in the rat. B-HT 920 potently inhibited the grooming elicited by a novel environment, whereas it stimulated the stretching-yawning syndrome. Pretreatment with the selective dopamine D2 receptor antagonist, sulpiride, reversed the phenomenon. When B-HT 920 was administered to rats before water immersion, it similarly antagonized total grooming; wet-dog shakes, detected in these same animals, were potently inhibited. Finally, B-HT 920 displayed inhibitory activity towards adrenocorticotropin hormone-induced excessive grooming. On the basis of these effects, the role of D2 receptor subtypes in the modulation of grooming is discussed.

Analysis of Variance↗

B-HT 920 stimulates feeding and antagonizes anorexia induced by ACTH and immobilisation.

The influence of immobilisation and i.c.v. injection of ACTH on feeding in rats was examined using a new experimental model. An X-maze with alternate open and covered arms, each baited with standard laboratory chow was used, where individual rats were placed and observed for 5 min. Two essential aspects of the behaviour towards food were considered, namely, tasting and feeding. A number of parameters were applied to demonstrate the anorectic activity of ACTH and immobilisation, in accordance with data obtained using classical procedures for feeding analysis. ACTH at the dose used did not modify rat exploratory activity and grooming in the X-maze without food pellets. In the same X-maze feeding test, B-HT 920, a selective agonist of dopamine D2 receptors and alpha 2-adrenoceptors, shown earlier to have anxiolytic- and antidepressive-like properties in rats, enhanced appetite and exerted anxiolytic activity when injected i.p. Pretreatment with B-HT 920 counteracted the restraint- and ACTH-induced effects. The results are discussed in the light of the relation between control of feeding and affective disorders. B-HT 920 activity seems to be of particular interest in view of its antagonism towards the anorexia elicited by two different agents reputed to have in common a key role in the stress-related disturbances of food intake.

Adrenergic alpha-Agonists↗

Effect of the D2-autoreceptor agonist B-HT 958 on both spontaneous and ACTH-induced stretching, yawning and grooming in the rat.

The D2 autoreceptor agonist B-HT 958, intraperitoneally injected into Wistar male rats in a novel environment, significantly increased stretching and yawning (SY) while inhibiting grooming. Pretreatment with the D2 antagonist sulpiride reversed these effects, antagonizing SY and restoring grooming. Similarly, when B-HT 958 was administered to rats in their home cages, it elicited SY and abolished grooming; moreover, when administered before the i.c.v. injection of adrenocorticotropin hormone, dose-dependently enhanced SY and strongly antagonized the typical syndrome of intensified grooming induced by the peptide. The possible relationship between SY and grooming and the involvement of D2 autoreceptors are discussed.

Adrenergic alpha-Agonists↗

Effects of the dopamine D2 agonists lisuride and CQ 32-084 on rat feeding behaviour.

The influence on rat-feeding behaviour of lisuride and CQ 32-084, agonists at dopamine D2 receptors, was examined using two procedures. In a first series of experiments, the apparatus was an X-maze baited with food pellets where individual fasted rats were observed for 5 min. A number of parameters were recorded: latency to tasting and feeding, interval between tasting and feeding, total feeding time, and total grooming time. Lisuride (0.05 and 0.1 mg/kg) and CQ 32-084 (0.05 and 0.5 mg/kg) behaved as stimulants of eating; lisuride (0.4 mg/kg) inhibited the phenomenon. Both drugs always antagonized grooming. Subsequently, when food intake was determined in the home cages of fasted animals lisuride reduced feeding at all doses during the first hour after treatment, while CQ 32-084 had no effect. The data show that the two compounds display different activity on ingestive behaviour according to the dose and experimental model used. Discussion centres on the possible dependence of feeding enhancement in the X-maze on the anxiolytic activity exerted by low D2 autoreceptorial doses.

Animals↗

Production of human to mouse xenografts by umbilical cord blood.

Utilizing human umbilical cord blood, it has been possible to create in irradiated animals a human to mouse xenograft. To facilitate hematopoietic reconstitution, SJL/J mice, which are functionally low in natural killer (NK) cells, were treated with anti-Asialo GM1 antibodies (anti-NK) and irradiation prior to injection of cord blood mononuclear cells. In contrast, SJL/J mice with the "beige" (bg/bg) mutation, which confers a functional NK cell deficiency, required only irradiation for successful transplantation. Human cells, detected by means of DNA probes, were demonstrated in the lungs and lymph nodes of irradiated animals up to 6 months after injection of the human cord blood cells.

Animals↗

NPY-induced inhibition of male copulatory activity is a direct behavioural effect.

In adult, sexually-experienced male rats, the intracerebroventricular injection of NPY caused a dose-related inhibition of copulatory behaviour, all parameters (mount, intromission and ejaculation latencies, mount and intromission frequencies, mean inter-intromission interval, post-ejaculatory interval) being significantly worsened at the dose of 8 micrograms/rat. Since rats were deprived of food during the behavioural test, it is concluded that inhibition of sexual behaviour is a 'true', direct behavioural effect of NPY, not due to a shift towards increased feeding.

Animals↗