Biomedical subjects

D Giuliani

Publications and source records attributed to D Giuliani.

At least 19 recordsLinked to original sources

PubMed2006

Reactive oxygen species, dietary restriction and neurotrophic factors in age-related loss of myenteric neurons.

We have studied the mechanisms underlying nonpathological age-related neuronal cell death. Fifty per cent of neurons in the rat enteric nervous system are lost between 12 and 18 months of age in ad libitum (AL) fed rats. Caloric restriction (CR) protects almost entirely against this neuron loss. Using the ROS-sensitive dyes, dihydrorhodamine (DHR) and 2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid (HPF) in vitro, we show that the onset of cell death is linked with elevated intraneuronal levels of reactive oxygen species (ROS). Treatment with the neurotrophic factors NT3 and GDNF enhances neuronal antioxidant defence in CR rats at 12-15 months and 24 months but not in adult or aged AL-fed animals. To examine the link between elevated ROS and neuronal cell death, we assessed apoptotic cell death following in vitro treatment with the redox-cycling drug, menadione. Menadione fails to increase apoptosis in 6-month neurons. However, in 12-15mAL fed rats, when age-related cell death begins, menadione induces a 7- to 15-fold increase in the proportion of apoptotic neurons. CR protects age-matched neurons against ROS-induced apoptosis. Treatment with neurotrophic factors, in particular GDNF, rescues neurons from menadione-induced cell death, but only in 12-15mCR animals. We hypothesize that CR enhances antioxidant defence through neurotrophic factor signalling, thereby reducing age-related increases in neuronal ROS levels and in ROS-induced cell death.

Aging↗

PubMed2004

Effects of ketamine anesthesia on central nociceptive processing in the rat: a 2-deoxyglucose study.

Ketamine is a dissociative anesthetic with complex actions on the CNS. We investigated here the effects of ketamine anesthesia on somatosensory processing in the rat spinal cord, thalamus, and cerebral cortex, using the quantitative 2-deoxyglucose mapping technique. Unanesthetized or ketamine-anesthetized male Sprague-Dawley rats received a s.c. injection of a dilute formaldehyde solution (5%, 0.08 ml) into a forepaw, inducing prolonged noxious afferent input, or an equal volume of isotonic saline as a control stimulus. The 2-deoxyglucose experiments started 30 min after the injection. In the cervical enlargement of the spinal cord, ketamine had no significant effect on glucose metabolic rates in saline-injected animals, whereas it prevented the metabolic increases elicited by prolonged noxious stimulation in unanesthetized animals. At the thalamic level, ketamine increased glucose uptake in both saline- and formalin-injected rats in the lateral posterior, lateral dorsal, medial dorsal, gelatinosus, antero-ventral and antero-medial thalamic nuclei, whereas it decreased metabolic activity in the ventro-basal complex. At the cortical level, the drug increased metabolic activity in both control and formalin groups in the lacunosus-molecularis layer of the dorsal hippocampus, posterior parietal, retrosplenial, cingulate and frontal cortex; significant metabolic decreases were found in the CA1 region of the dorsal hippocampus and in the parietal 1 and 2 cortical areas. In the investigated brain regions, ketamine did not abolish noxious-evoked increases in glucose uptake, which were in fact enhanced in the forelimb cortex and in the lacunosus-molecularis layer of the hippocampus. The dissociation between the spinal and supraspinal effects of ketamine suggests a specific antinociceptive action on spinal circuits, in parallel with complex changes of the activity of brain circuits involved in somatosensory processing. More generally, this study shows that functional imaging techniques are able to quantitatively assess the effects of anesthetic drugs on nociceptive processing at different levels of the neuraxis.

Analysis of Variance↗

PubMed2002

Influence of sildenafil on central dopamine-mediated behaviour in male rats.

Two experiments were performed to evaluate the effects of sildenafil on spontaneous or dopamine agonist-induced behaviour in male rats. Data obtained in experiment 1 show that oral administration of the drug, at 1 mg/kg, significantly increased the occurrence of penile erections, anogenital self-grooming and homosexual mounting in grouped sexually-experienced, but not inexperienced, animals. In experiment 2, pre-treatment with sildenafil (0.5, 1 or 10 mg/kg) dose-dependently modified several behavioural signs, centrally evoked by the D2/D3 dopamine agonists, 7-OH-DPAT or B-HT 920 (both at 0.1 mg/kg), in experimentally naive male rats. While sildenafil at 1 mg/kg significantly increased the number of penile erection and stretching-yawning episodes induced by 7-OH-DPAT or B-HT 920, at 10 mg/kg it elicited low stereotyped behaviour, antagonizing stretching-yawning and sedation in 7-OH-DPAT treated rats. Discussion centres on the modulatory activity of sildenafil on central dopaminergic pathways and, possibly, on nitric oxide production.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2002

Influence of sildenafil on copulatory behaviour in sluggish or normal ejaculator male rats: a central dopamine mediated effect?

The present study investigates the effects induced by sildenafil (1 mg/kg, p.o.) and the dopamine agonist, SND 919 (0.1 mg/kg, i.p.) on copulatory behaviour of male rats, categorized, on the basis of seven consecutive mating pre-tests, as sluggish and normal ejaculators (SE and NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and ejaculatory mechanisms of copulation. It appears that, although it induced a facilitatory effect on ejaculation of all rats, similarly to SND 919, the lowering of ejaculatory threshold was achieved by means of a reduction of mount frequency and intromission frequency in SE and NE groups, respectively. Differently from SND 919, sildenafil increased sexual arousal, diminishing post ejaculatory interval in SE animals and inter-intromission interval in both SE and NE rats. As the dopamine antagonist, (-)eticlopride (0.02 mg/kg, s.c.), significantly inhibited sildenafil-induced enhancement of sexual arousal in SE rats, it is suggested that the drug acts both peripherally and centrally.

Animals↗

PubMed2002

Modulatory activity of sildenafil on copulatory behaviour of both intact and castrated male rats.

The first experiment of the present study investigates the effects induced by sildenafil (1 or 10 mg/kg po) on the copulatory behaviour of intact male rats, categorized, on the basis of seven consecutive mating pretests, as sluggish or normal ejaculators (SE or NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and the ejaculatory mechanisms of copulation, diminishing ejaculation latency in both categories and increasing copulatory efficacy in SE rats; in addition, it reduced the inter-intromission interval in both SE and NE animals and the post-ejaculatory interval only in SE animals. The second experiment, conducted on rats 3 weeks after their castration, shows that sildenafil alone (1 or 10 mg/kg) did not modify copulatory failure. However, 3 months after castration, and 24 h after the last injection of testosterone (25 microg/kg sc) given twice weekly for 4 weeks, sildenafil (1 or 10 mg/kg) ameliorated rat copulatory performance.

Animals↗

PubMed2001

Hu 210: a potent tool for investigations of the cannabinoid system.

The synthetic compound HU 210 displays a multiplicity of biochemical, pharmacological, and behavioral effects, most of which have been demonstrated to be dependent on a selective agonistic activity at CB(1) and CB(2) cannabinoid receptors and to involve the main neurotransmitter systems. Results obtained in various studies suggest a potential clinical application of this highly potent drug (e.g., as antipyretic, antiinflammatory, analgesic, antiemetic, and antipsychotic agent) as well as its usefulness in research aimed to develop a better understanding of the involvement of the endogenous cannabinoid system in a number of physiopathological functions.

Analgesia↗

PubMed2000

Effects of the cannabinoid receptor agonist, HU 210, on ingestive behaviour and body weight of rats.

The effect of the synthetic cannabinoid receptor agonist, (-)11-hydroxy-Delta(8)-tetrahydrocannabinol-dymethylheptyl (HU 210), on rat body weight and eating and drinking behaviour was examined. In Experiment 1, the drug (25, 50 or 100 microg/kg), sub-chronically administered for 4 days, produced a dose- and time-dependent loss of body weight that, at the highest dose, was not regained by 7 days after the drug was stopped, and remained markedly below that of vehicle-treated animals. In Experiment 2, food and water intakes, which were evaluated in fasted rats, tested as in Experiment 1, were significantly inhibited only by the dose of 100 microgram/kg, and this effect was still present 7 days after the last injection of the drug. The possibility that the effects observed are not directly dependent on the control of appetite and might be ascribable to stress-related phenomena is discussed.

Animals↗

PubMed2000

The cannabinoid agonist HU 210 modifies rat behavioural responses to novelty and stress.

Experiments were performed on groups of rats after acute and sub-chronic treatment (once daily for 9 days) with the cannabinoid agonist HU 210 (25-100 microg kg(-1), i.p.) as well as 24 h and 7 days after the last drug injection. The animals underwent three behavioural tests in novel environments. In the observation cages (Test 1), rat locomotor activity was found to be dose-dependently reduced after acute and sub-chronic treatment at all doses and virtually unchanged during abstinence; grooming was potently inhibited by acute treatment but potentiated by the sub-chronic one at doses of 50 and 100 microg kg(-1), the effect of the higher dose persisting after 24 h and 7 days abstinence. Vocalization in animals in response to a tactile stimulus was highest after HU 210 at 100 microg kg(-1) in all experimental modes except after 7 days abstinence. In the X-maze (Test 2), sub-chronic HU 210 dose- dependently enhanced rat natural aversion for open arms, and this behaviour persisted during abstinence after the highest dose. Grooming in the X-maze was completely absent in rats acutely injected with HU 210 but potentiated in those sub-chronically treated or abstinent. In the swimming test (Test 3) rats sub-chronically treated at 50 and 100 pg kg(-1) displayed relevant wall-hugging and the same occurred 24 h after last injection. On the whole, our results are indicative of an anxiogenic-like effect of sub-chronic HU 210 at high doses and reflect the persistence of enhanced emotional response to novel environments when the treatment is discontinued.

Animals↗

PubMed1999

Influence of the cannabinoid agonist HU 210 on cocaine- and CQP 201-403-induced behavioural effects in rat.

Acute injection of the cannabinoid agonist HU 210 (6.25-100 microg/kg, i.p.) dose-dependently inhibited rat locomotor activity and rearing, while subchronic treatment with the drug (once daily for 7 days) at the same doses only diminished locomotion. Acute but not subchronic administration of HU 210 (12.5-50 microg/kg, i.p.) potently counteracted acute and subchronic cocaine (15 mg/kg, i.p.)-induced hyperlocomotion and enhanced rearing. The acute cannabinoid (6.25-100 microg/kg, i.p.) also inhibited locomotor activity, stereotyped behaviour and shaking elicited by the D1/D2 agonist CQP 201-403 (500 microg/kg, i.p.). On the contrary, subchronic treatments with HU 210 enhanced CQP 201-403-induced locomotor activity and potently stimulated escape attempts. Discussion centers on the influence of cannabinoids on experimental models of psychosis.

Animals↗

PubMed1999

Cannabimimetic activity in rats and pigeons of HU 210, a potent antiemetic drug.

Preliminary behavioral experiments in rats with the cannabinoid agonist HU 210 (12.5-100 microg/kg i.p.) showed that it has a potent cannabimimetic profile similar to that of delta9THC; the drug dose dependently depressed locomotor activity, rearing, and grooming and elicited vocalization and circling at the highest doses. In subsequent studies on pigeons, HU 210 (12.5-50 microg/kg s.c.) confirmed its sedative effects; it also afforded protection against vomiting induced by cisplatin (7.5 mg/kg i.v.) and emetine (20 mg/kg s.c.) and emetine-induced head shake.

Animals↗

PubMed1999

Learning impairment produced in rats by the cannabinoid agonist HU 210 in a water-maze task.

To ascertain whether the cannabinoid agonist HU 210 (25, 50, or 100 microg/kg, IP) influences rat spatial learning, water-maze performance was examined in the place (hidden platform)--and cue (visible platform)--versions of the Morris water maze. In addition, other unlearned behaviors were examined, namely, vocalization and wall hugging during the place task, and motor abilities during a motor test battery. The results obtained show that HU 210 at 50 or 100 microg/kg (once daily for 4 days, 60 min before a daily session) impaired learning in the place version but not in the cue one; wall hugging and enhanced vocalization were also displayed by the animals in the fourth session. Motor activity was compromised by the same treatment schedule. When the drug was discontinued, the effects produced by HU 210 at 50 microg/kg reversed in 3 days, while disruption of acquisition and vocalization caused by HU 210 at 100 microg/kg remained after 7 days' abstinence. Discussion centers on the possible specific cognitive mechanisms affected by the drug and on aspecific factors (i.e., anxiety-like state), which may contribute to the impairment of spatial learning.

Animals↗

PubMed1999

CNS pattern of metabolic activity during tonic pain: evidence for modulation by beta-endorphin.

CNS correlates of acute prolonged pain, and the effects of partial blockade of the central beta-endorphin system, were investigated by the quantitative 2-deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin-induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti-beta-endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin-injected rats, pretreated with anti-beta-endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo-cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for beta-endorphin in central networks that process somatosensory inputs.

Animals↗

PubMed1997

Involvement of dopamine D2 receptors in the effect of cocaine on sexual behaviour and stretching-yawning of male rats.

The effect of cocaine (7.5, 15 and 30 mg/kg) administered in acute or subchronic mode, on the mating behaviour of sexually active male rats varied in a dose- and mode-dependent manner. Regardless of mode of treatment, 30 mg/kg markedly impaired the rats copulatory ability and impairment continued for a week after suspension of subchronic treatment. An acute dose of 15 mg/kg reduced intromission frequency, while in subchronic mode it also reduced ejaculation latency. Mount frequency was increased by 7.5 and 15 mg/kg, but only on first injection. In the case of sexually-naive male rats, acute administration of cocaine (3-30 mg/kg) stimulated penile erections at 7.5 mg/kg and motor hyperactivity at all doses. (-) Eticlopride (0.025 and 0.05 mg/kg), a DA D2 antagonist, counteracted cocaine-induced motor hyperactivity but not penile erection, which it enhanced. (-) Eticlopride at the same doses also antagonized cocaine potentiation of lisuride (0.2 mg/kg)-induced behavioural effects. When male rats treated with subchronic cocaine (15 mg/kg) were injected with the DA D2 agonist SND 919 (0.1 mg/kg), they displayed a more marked stretching-yawning behaviour than control animals receiving SND 919 at the same dose. The involvement of DA D2 receptors in cocaine-induced effects is suggested.

Animals↗

PubMed1997

Involvement of dopamine receptors in the antipsychotic profile of (-) eticlopride.

The present study was performed to assess the effects exerted by the dopamine (DA) D2/D3 antagonist (-) eticlopride on rodent behavioral models considered to be predictive of antipsychotic activity, namely, antagonism toward DA agonist-induced stereotyped behavior (SB), and ketamine-and cocaine-induced hypermotility. (-) Eticlopride (10-50 micrograms/kg) dose-dependently inhibited SB elicited by SND 919 (10 mg/kg), CQP 201-403 (0.5 mg/kg), and 7-OH-DPAT (5 mg/kg); moreover, it significantly counteracted the hypermotility induced in rats and mice by ketamine (5 and 10 mg/kg). When (-) eticlopride was injected before cocaine (15 mg/kg) either acutely or subchronically administered in male rats, it also potently antagonized the hypermotility typically induced by the drug. These results are discussed in the light of putative D2/D3 receptor involvement, and are considered as predictive of antipsychotic potential.

Animals↗

PubMed1997

Effects of (-)eticlopride and 7-OH-DPAT on the tail-suspension test in mice.

The dopamine (DA) D2/D3 antagonist (-)eticlopride (0.02, 0.05 and 0.1 mg/kg), dose-dependently increased immobility in the mouse tail-suspension test. Chronic treatment with the same compound (0.05, 0.1 mg/kg, x 14 days) produced a different effect, decreasing immobility when animals were tested 24 h after the last injection. The DA D3 agonist, 7-OH-DPAT, acutely administered before the same test, behaved biphasically, increasing and decreasing mice immobility at low (0.05 and 0.1 mg/kg) and high (1 and 2 mg/kg) doses, respectively. Chronically administered 7-OH-DPAT reduced the immobility time at 2 mg/kg but not at 0.1 mg/kg. These effects, coupled with measurements of locomotor activity and evaluation of mice behaviour in different conditions, are discussed in the light of putative DA involvement in depressive states and are considered as predicting antidepressant potential.

Animals↗

PubMed1996

Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and related derivatives as dopamine receptors ligands.

The present work reports the synthesis of enantiomeric pairs of the trans-2-amino-6-hydroxy-1-phenyl-2,3-dihydro-1H-indene [(+)-14a, (-)-14a] and trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1 H-indene [(+)-14b, (-)-14b] and their N,N-di-n-propyl [(+)-and (-)-15a,b], N-methyl-N-allyl [(+)-and (-)-16a,b], and N-methyl-N-n-propyl [(+) and (-)-17a,b] derivatives obtained by a combination of stereospecific reactions and optical resolution. The new compounds were evaluated for their affinity at the dopamine D1 and D2 receptors. The amines (+)- and (-)-14a, incorporating the D1 pharmacophore 2-phenyl-2-(3-hydroxyphenyl)ethylamine in a trans extended conformation, and their derivatives displayed D1 and D2 affinity in the nanomolar range. On the other hand, the enantiomers (+)- and (-)-14b, (+)- and (-)-15b displayed high affinity and selectivity for the D1 receptor. In a preliminary behavioral study on rats (+)-14b, and to a greater extent (+)-15b, promoted episodes of intense grooming, thus indicating that they act as central D1 agonists. The trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1H-indenes (+)-14b and (+)-15b represent selective D1 agonists lacking a catechol group, which should meet the prerequisites for a central nervous system penetration.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

Behavioral effects induced by the dopamine D3 agonist 7-OH-DPAT in sexually-active and -inactive male rats.

The present study investigates the effects induced by the putative DA D3 agonist 7-OH-DPAT (0.1 and 1 mg/kg, s.c.) on: (1) the sexual behavior of male rats, categorized on the basis of seven consecutive mating pre-tests as sexually-active (SA) and sexually-inactive (SI); and (2) stretching-yawning, penile erection, sedation and stereotyped behavior of the same animals. The data obtained show that 7-OH-DPAT at both doses modifies the copulatory pattern of SA rats, facilitating ejaculation mechanisms, but fails to increase the sexual drive of the animals as is evident from the ineffectiveness in SI rats. The second major finding is that the two groups of rats, which are markedly different as regards sexual typology, exhibit different behavioral responses to 7-OH-DPAT.

Animals↗

PubMed1996

Influence of eticlopride on cocaine- and DA D2 agonist-induced behavioral effects in rats.

The influence of the DA D2 antagonist (-) eticlopride on cocaine- and DA D2 agonist-induced behavioral effects was investigated by means of two series of experiments, in rats. In the first 10-day series, coadministration of (-) eticlopride (10 and 50 micrograms/kg, SC) always potently inhibited cocaine (15 mg/kg, IP)-induced hypermotility but did not modify the penile erection (PE)-enhancement produced by the drug at the first injection; it actually counteracted the inhibitory effect of subchronic cocaine on PE. In the second series, (-) eticlopride, at the same doses, antagonized PE elicited by various DA D2 agonists at nonstereotyping doses; when, along with PE, stereotyped behavior was induced, only the latter was inhibited by (-) eticlopride, which even increased PE.

Animals↗