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Biomedical subjects

M Morelli

Publications and source records attributed to M Morelli.

At least 91 records · Page 5Linked to original sources
PubMed1992

Priming as a model of behavioural sensitization.

Repeated exposure to drugs acting as direct or indirect stimulants of central dopamine transmission results in sensitization to their behavioural stimulant properties (behavioural sensitization). Priming provides a simple model of behavioural sensitization particularly suitable for studies of its neural and molecular mechanisms. The results obtained to date indicate that priming results in an increased responsiveness of postsynaptic dopamine receptor mechanisms in the caudate nucleus, possibly due to an increased affinity of the D-1 receptor for its agonist.

Animals↗
PubMed1992

Opposite effects of NMDA receptor blockade on dopaminergic D1- and D2-mediated behavior in the 6-hydroxydopamine model of turning: relationship with c-fos expression.

In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway, I-dihydroxyphenylalanine (L-DOPA) induces contralateral turning through activation of denervated D1 and D2 receptors. Blockade of N-methyl-D-aspartate (NMDA) receptors by the noncompetitive antagonist (+)MK-801 (0.1 mg/kg, i.p.), potentiated L-DOPA-induced contralateral turning. In 6-OHDA lesioned rats, selective agonists of D1 (SKF 38393, CY 208-243) or D2 (LY 171555) receptors also induce contralateral turning; however, (+)MK-801 pretreatment, although markedly potentiating D1, almost completely inhibited D2-mediated turning. The potentiation of SKF 38393-induced contralateral turning by MK-801 was stereospecific and was observed also with the noncompetitive NMDA antagonist phencyclidine, and with the competitive antagonist CPP. Administration of the D1 antagonist SCH 23390 (0.1 mg/kg s.c.) blocked (+)MK-801-induced potentiation of L-DOPA contralateral turning, confirming the D1 nature of the effects observed. Expression of the early gene c-fos in the caudate-putamen (CPu) is known to be activated by stimulation of supersensitive D1 receptors. Immunohistochemical studies on c-fos revealed sparse c-fos positive nuclei in the lesioned CPu after 1.5 mg/kg of SKF 38393, whereas after combined administration of (+)MK-801 and SKF 38393, dense labeling of nuclei was obtained in the dorso-lateral aspect of the CPu. Therefore, blockade of NMDA receptors acts synergistically with D1 and antagonistically with D2 receptor stimulation in the 6-OHDA model of turning, suggesting that different neuronal pathways are involved in the mediation of D1 and D2 responses.

Animals↗
PubMed1992

Functions of dopamine in the extrapyramidal and limbic systems. Clues for the mechanism of drug actions.

Dopamine (DA) is a neurotransmitter which modulates the transfer of information along fast-conducting pathways at the level of two main nodal points: the ventral striatum, composed by limbic areas (nucleus accumbens, tuberculum olfactorium) and the dorsal striatum, composed by extrapyramidal nuclei (caudate-putamen). These two subdivisions of the enlarged basal ganglia, are provided with different functions; accordingly, limbic DA plays an active role in goal-oriented (motivated) behaviour; instead, extrapyramidal DA is essential for execution of learned motor programs and its impairment results in the symptoms of Parkinson's disease. Various centrally acting drugs are able to interfere with DA transmission or with other neurotransmitter systems which interact with DA. Drugs of abuse owe their incentive properties to a preferential stimulation of DA transmission at the level of the limbic dopaminergic areas. On the other hand, drugs able to block glutamatergic transmission on NMDA receptors are able to selectively potentiate the action of DA at the level of a specific type of DA-receptors, the D-1 type. Knowledge of the role of DA in the brain can provide the basis not only for understanding the mechanism of drug action but also for developing new strategies for the treatment of drug abuse and extrapyramidal disorders.

Animals↗
PubMed1992

[Loco-regional analgesia with continuous peridural technique in labor. Evaluation of 4 years of experience].

The Authors report on the results of their experience using local-regional analgesia performed with the continuous peridural technique over four years of activity with 503 pregnant women. Protocols used over the years called for morphine-fentanyl association, but bupivacaine 0.25% plus fentanyl and bupivacaine 0.125% plus fentanyl mixtures were then employed. In order to evaluate the efficiency of this procedure, the following data were recorded for each patient undergoing the analgesia: duration of labor prior to the effect of the analgesia; time to reach complete dilatation from a 3 cm dilatation; the length of time of the expulsive phase; manifestation of side effects and complications; vacuum utilization. Furthermore, Apgar scores were taken for all newborn babies at 1st and 5th minutes. The data were then compared with those recorded for a group of women with the same obstetrical characteristics who were not treated with analgesia. The comparison showed that the length of time of the dilatation phase (from 3 to 10 cms) was significantly less in the group of treated patients, while the expulsive phase was basically similar in both groups, thus showing that labor mean time had significantly decreased in the group of patients treated with analgesia. The number of vacuum births was basically the same in both groups and comparable to the data available in the literature. These were practically no side effects or complications. In conclusion, our experience confirms the fact that this method is the most reliable in terms of safety, effectiveness and acceptability on the part of women compared to any other analgesic treatment employed during labor.

Adult↗
PubMed1991

Surgical treatment of cardiac arrhythmias.

This report describes 20 consecutive patients who underwent surgical procedures for treatment of cardiac arrhythmias. 16 patients have been operated for WPW syndrome, always using the epicardial approach, without extracorporeal circulation. Three patients underwent surgery for atrio-ventricular nodal reentrant tachycardia, using a discrete perinodal cryotreatment, during normothermic extracorporeal circulation. In one case we used cryoablation of the atrial myocardium below the coronary sinus to treat atrial flutter. This operation was performed under normothermic extracorporeal circulation. In our observations, there was no early or late death; postoperative complications developed in 1 patient (5%) due to pericarditis. Ablation of the AP was completely successful in all the cases (100%) operated for WPW as well as for AVNRT syndromes and atrial flutter.

Arrhythmias, Cardiac↗
PubMed1991

H-reflex modulation during manual muscle massage of human triceps surae.

An investigation of the effect of a six-minute manual muscle massage on the excitability of the spinal reflex pathway in 20 able-bodied subjects was undertaken. H-reflex recordings were obtained from the right soleus muscle, which was the site being massaged. Skin temperature and antagonist activity were monitored in an attempt to explain the changes observed in a previous study. The experimental paradigm chosen was an A-B-A interrupted-time series design consisting of two pretreatment, two treatment (massage), and two posttreatment conditions. H-reflex amplitudes recorded during both massage conditions (.76 +/- .58 mV, .76 +/- .61 mV) were significantly reduced (F5,90 = 69.04, p less than .01) in comparison to all other (before and after) conditions (2.58 +/- .75 mV, 2.56 +/- .71 mV, 2.82 +/- 1.14 mV, and 2.89 +/- .82 mV, respectively). This decrease could not be explained conclusively by changes in skin temperature, nerve conduction velocity, or antagonist recruitment, thus indicating a decrease in spinal reflex excitability attributed to massage. These findings also support our earlier report, which stated that H-reflex amplitudes are reduced only during the period of tissue manipulation, regardless of the duration of the massage.

Adult↗
PubMed1991

Positive and negative interactions in the behavioural expression of D1 and D2 receptor stimulation in a model of Parkinsonism: role of priming.

Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D1 and D2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D1 and D2 receptors, we examined the effect of selective D1 and D2 receptor blockade on the contralateral turning induced by the mixed D2/D2 agonist apomorphine in drug-naive and primed 6-hydroxydopamine-lesioned rats. In drug-naive rats, apomorphine induced a dose-related, apparently monophasic rotation curve. Administration of selective D1 (SCH 23390) or D2 (raclopride) antagonists abolished the contralateral turning induced by 0.1 mg/kg of apomorphine and partially inhibited that induced by 0.5 mg/kg. In primed rats low doses of apomorphine (0.05 mg/kg) induced an apparently monophasic contralateral turning which was reduced by D1 receptor blockade and completely abolished by D2 receptor blockade; a higher dose of apomorphine (0.1 mg/kg) instead elicited a biphasic (two-peak) pattern of rotation. After this dose of the agonist, blockade of D1 or D2 receptors abolished the second peak of rotation but, while D1 blockade reduced the total number of turns, D2 blockade failed to do so. Quantitative analysis of the interaction between D1 and D2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D1 and D2 receptors interact not only positively but also negatively. After higher doses of apomorphine, both negative and positive interactions take place sequentially during the time-course of apomorphine action and provide a clue for explaining the two-peak pattern of rotation observed after apomorphine in rats previously exposed to the drug.

Animals↗
PubMed1991

Effects of massage on alpha motoneuron excitability.

The purpose of this study was to investigate the specificity of the effects of massage (petrissage) on spinal motoneuron excitability as measured by changes in the peak-to-peak amplitude of H-reflex recordings. H-reflexes (and M-responses) were recorded from the distal aspects of the right triceps surae muscle of 8 men and 8 women, aged 20 to 37 years, with no neuromuscular impairments of the lower extremities. The H-reflexes were recorded during five control and four experimental conditions (20 trials at each condition). The control conditions (C1-C5) preceded and followed each experimental condition, providing a measure of the stability of the H-reflex. Each experimental condition consisted of a 4-minute period of massage of the ipsilateral and contralateral triceps surae and hamstring muscle groups (ITS, CTS, IHS, and CHS, respectively). The mean peak-to-peak amplitude of the H-reflex was found to be stable (range = 1.91-1.95 mV) across the five control conditions. H-reflex amplitudes recorded during the experimental conditions indicate that massage of the ITS resulted in a reduction of the H-reflex (0.83 mV) in comparison with the pretest control condition (C1) and the remaining experimental conditions (range = 1.77-2.23 mV). This difference was significant, and subsequent Newman-Keuls tests indicated a specificity of the effects of massage on the muscle group being massaged. [Sullivan SJ, Williams LRT, Seaborne DE, Morelli M. Effects of massage on alpha motoneuron excitability.

Adult↗
PubMed1990

Changes in the D1 receptor-adenylate cyclase complex after priming.

The D1 agonist, SKF 38393, failed to induce contralateral turning in drug-naive rats lesioned unilaterally with 6-hydroxydopamine from 17 days. Priming with a dopamine agonist, such as the D2 agonist, LY 171555, three days before, made SKF 38393 fully effective in inducing contralateral turning. Analysis of D1 receptor binding in striata of drug-naive and primed rats showed no change in the Bmax and Kd. In contrast, dopamine-stimulated adenylate cyclase showed a decrease in its Km for dopamine in the lesioned side of primed rats as compared with drug-naive rats. Thus, priming appears to elicit changes at the level of the transduction mechanism of D1 receptors rather than in the D1 recognition site itself.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Stereospecific blockade of N-methyl-D-aspartate transmission by MK 801 prevents priming of SKF 38393-induced turning.

In rats unilaterally lesioned with 6-hydroxydopamine, the D-1 agonist SKF 38393 (3 mg/kg SC) induced contralateral turning only after priming with a dopaminergic agonist such as apomorphine. Administration of the N-methyl-D-aspartate receptor antagonist (+) MK 801 (0.1 mg/kg IP) 15 min before apomorphine (0.1 mg/kg SC) prevented the ability of apomorphine to act as a primer while potentiating its acute contralateral turning effects. The inactive isomer (-) MK 801 was without effect. The results indicate that the N-methyl-D-aspartate receptor exerts a permissive role on priming.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Quantitative autoradiographical analysis of the age-related modulation of central dopamine D1 and D2 receptors.

Quantitative autoradiography of [3H]SCH 23390 and [3H](-)-sulpiride binding was performed in the brain of rats of various ages (3, 11 and 24 months) in order to study the changes in D1 and D2 receptor density with age. Binding of [3H]SCH 23390 in the caudate-putamen decreased progressively and markedly at rostral levels in 11- and 24- compared with 3-month-old rats (max. decrease -63%) while at caudal levels significant decrease was observed only in 24-month-old rats. [3H](-)-Sulpiride binding progressively decreased during aging in the caudate-putamen at rostral levels and the decrease was more pronounced laterally (-70% at 24 months), while at caudal levels no significant decrease was observed. D1 and D2 binding sites also decreased in the nucleus accumbens and olfactory tubercle of aged rats, while in the substantia nigra only the D1 receptors appeared to be modified with aging. No change was found in the entopeduncular nucleus, amygdala, frontoparietal, suprarinal-prefrontal and anterior cingulate cortex. The results indicate that the age-associated decrease of D1 and D2 receptors is not widespread, being confined to dopaminergic areas with high density of dopamine receptors.

Aging↗
PubMed1990

Disodium cromoglycate versus diet in the treatment and prevention of nickel-positive pompholyx.

In some cases that have been diagnosed as contact allergy to nickel, there are repeated cutaneous eruptions of pompholyx, even in areas with no direct contact with the metal. The possible alimentary origin of dyshidrotic eczema should be considered when deciding on therapy. We have collected the clinical data for 24 patients with dyshidrotic eczema caused by nickel, to evaluate the benefit of a low-nickel diet versus treatment with oral disodium cromoglycate, comparing both objective and subjective symptoms. A low-nickel diet does not improve these patients but those treated with DSCG reacted better, from both objective and subjective point of view, than either the controls or the patients treated by diet. We next did intestinal permeability tests before therapy and after 15 days of treatment. We found that nickel uptake diminishes simultaneously with the reduction of absorption through the smaller aqueous "pores". This phenomenon was greatest after DSCG. We suggest that DSCG can help selected cases of pompholyx.

Adult↗
PubMed1989

Substantia nigra as a site of origin of dopamine-dependent motor syndromes induced by stimulation of mu and delta opioid receptors.

Opioid agonists having different affinity for delta and mu receptors were injected bilaterally in the substantia nigra (SN) of rats. The selective agonist of mu receptors N-MePhe3,-D-Pro4 morphiceptin (PLO 17) produced a stereotyped behavior characterized by stereotyped sniffing and gnawing antagonized by the irreversible antagonist of mu receptors beta-funaltrexamine. In contrast, bilateral intranigral injection of the selective delta agonist D-Pen2,D-Pen5 enkephalin (DPDPE) elicited dose-dependent exploratory behavior and rearing but failed to produce gnawing. The behavioral syndrome induced by DPDPE was significantly reduced by the selective delta antagonist ICI 174,864. Naloxine, a non-selective opioid antagonist, antagonized the effects of both compounds. SCH 23390 and haloperidol, two antagonists of dopaminergic D1 and D2 receptors, respectively, blocked the effects of PLO 17 and DPDPE. The results indicate that stimulation of specific opioid receptor types in the SN elicits specific behavioral syndromes and suggest that the SN might be the site of origin of certain items of the behavioral syndrome evoked by systemic opiates. These items might be mediated by activation of dopaminergic neurons of the ventral mesencephalon.

Animals↗
PubMed1989

Time and dose dependence of the 'priming' of the expression of dopamine receptor supersensitivity.

The D-1 receptor agonist, SKF 38393 (2 mg/kg s.c.), failed to elicit contralateral turning when administered to drug-naive rats 17 days after unilateral 6-hydroxydopamine (6-OHDA) lesioning of the medial forebrain bundle, while it elicited intense contralateral turning 90 days post-lesioning. On the other hand the D-1/D-2 receptor agonist, apomorphine (0.1 mg/kg s.c.), induced contralateral turning in drug-naive rats lesioned 14 days earlier and made the administration of SKF 38393 (2 mg/kg s.c.) 3 days later effective to evoke contralateral turning ('priming'). The effectiveness of apomorphine as a primer of SKF 38393-induced turning depended critically on the interval between the administration of the two agonists. Effectiveness was minimal after 3 h and increased after 6-12 h, peaked at 72 h and was reduced after 10 days. The D-2 receptor agonist, LY 171555 (0.2 mg/kg s.c.), was also effective as a primer of SKF 38393-induced contralateral turning and this effect also was dependent upon the interval between priming and SKF 38393 administration. Moreover, priming was dependent on the dose of drug used as primer and on the dose of SKF 38393 used as a challenge. In contrast to SKF 38393, priming was unable to make effective a dose of LY 171555 that was ineffective in drug-naive rats, suggesting that LY 171555 affects D-1-dependent turning to a greater extent than D-2-dependent turning. The results indicate that the priming phenomenon is rather strictly time- and dose-dependent.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Electrophysiological evidence for interhemispheric transmission of visual information in man.

1. Electrophysiological evidence is presented of interactions between two stimuli (sinusoidal gratings of equal spatial frequency but different contrast, phase-reversed sinusoidally at different temporal frequencies) located on opposite side of, and within a few degrees from, the vertical meridian. 2. These interactions are revealed by a depression of the cortical visual evoked potential (VEP) evoked by the grating of lower contrast in the presence of the grating of higher contrast. They are similar to, albeit weaker than, those obtained with superimposed asynchronously modulated gratings. 3. The VEP reduction occurs also if the stimuli are presented dichoptically. 4. It does not occur if the gratings are located one above the other either on the same or on opposite sides of the vertical meridian. 5. The strength of the VEP reduction depends on the relative contrast of the two gratings and vanishes for spatial frequencies beyond 4 cycles/deg and temporal frequencies of the high-contrast grating beyond 10 Hz. 6. The results are in agreement with data on visual callosal connections in animals and confirm previous psychophysical findings (Berardi & Fiorentini, 1987) indicating the particular properties of the interhemispheric cross-talk between symmetric regions of the visual field astride the vertical meridian in man.

Brain↗