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Biomedical subjects

F Melis

Publications and source records attributed to F Melis.

At least 37 records · Page 2Linked to original sources

Chronic ethanol consumption in rats: correlation between memory performance and hippocampal acetylcholine release in vivo.

The effects of chronic alcohol consumption on memory performance and hippocampal acetylcholine release in vivo were investigated in rats. Rats were allowed to drink 25% (v/v) ethanol solution as the only source of fluid for nine consecutive months, whereas control rats received only tap water. Memory performance was tested by the acquisition of shuttle box active and passive avoidance. Chronic ethanol-consuming rats were not impaired in the acquisition of the active avoidance response task, whereas in the passive avoidance task, latency scores of treated rats were significantly lower than in controls. The basal release of acetylcholine in freely moving rats, assessed by the microdialysis technique, was significantly decreased in ethanol-treated rats. Impairment in memory performance, as assessed in the passive avoidance task, was significantly correlated with hippocampal acetylcholine release in vivo.

Acetylcholine↗

Trigeminal motoneuron responses to vestibular stimulation in the guinea pig.

Experiments performed in the guinea pig were aimed at evaluating the effect of electric or caloric stimulations of the vestibular afferents on the electrical activity of the jaw-closing and jaw-opening trigeminal motoneurons. Results showed that masseter and digastric motoneurons mainly responded to vestibular ampullar activation with excitatory responses, with latencies being shorter for contralateral than ipsilateral ampullar stimulation. Differences in latencies between the jaw-closing and jaw-opening trigeminal motoneurons were observed: the masseter motoneurons constantly responded about 2 msec earlier than the digastric motoneurons. These results suggest that the vestibular-trigeminal relationship is quite complex and uses multiple systems to connect the vestibular apparatus with the trigeminal motor nuclei. From the functional point of view, the vestibular-trigeminal relationship may play a role in the dynamic control of the jaw muscle tone during head movements.

Animals↗

Effects of the calcium channel antagonist darodipine on ethanol withdrawal in rats.

The effect of the dihydropyridine calcium channel antagonist, darodipine, on ethanol withdrawal syndrome was examined in rats made dependent on ethanol by repeated ethanol administration for six consecutive days. Chronic co-administration of darodipine prevented the severity of ethanol withdrawal signs in a dose-dependent fashion. By contrast, acute administration of darodipine during the ethanol withdrawal phase was ineffective in reversing the withdrawal symptoms. The results suggest that the presence of darodipine in the central nervous system during the adaptative responses to ethanol is necessary to reduce the severity of the withdrawal syndrome. They also provide further evidence for a potential clinical usefulness of dihydropyridine calcium channel blockers in treatment of ethanol withdrawal.

Animals↗

Olfactory influence on tongue activity.

Recent findings have shown that olfactory stimulation by brief puffs of air odorized with amyl acetate induces several patterns of response in rabbit hypoglossal neurons. It has been argued that the functional role of the olfactory input may be the modulation of tongue muscular tone during the oral phase of digestion. In the present research, the peripheral effect of olfactory-hypoglossal modulation was analyzed. Both the spike traffic along the fibers of the hypoglossal nerve and the electromyographic activity of single tongue muscles (genioglossus, styloglossus, superior longitudinal and hyoglossus) were recorded before, during and after olfactory stimulation. Results showed that brief puffs of air odorized with amyl acetate induced a significant change in the efferent volleys along the hypoglossal nerve, as well as a substantial modulation of tongue muscle activity. Olfactory stimulation induced a significant increase in the spontaneous activity of both type I and type II genioglossal fibers; excitation followed by inhibition both in tonic and phasic styloglossal fibers; excitatory responses in tonic and phasic superior longitudinal fibers and short-lasting excitatory responses in the hyoglossal fibers. The diverse patterns of activation of the tested muscle and the significant differences between fibers, tonically or phasically controlled by the XIIth neurons, indicate that olfaction may be strongly involved in tongue reflex regulation. Different functional hypothesis are discussed about the role played by olfaction in the economy of tongue muscle activity.

Action Potentials↗

Long-term potentiation within the cat motor cortex.

Synaptic plasticity in the motor cortex of anesthetized cats was examined using intracellular recording and labeling techniques. Intracortical microstimulation (ICMS) was delivered in the superficial layers and recordings were made from cells in layer V. When the neuron responded to ICMS with an excitatory postsynaptic potential (EPSP), tetanic ICMS (100-200 Hz, 10-20 s) was delivered to the same site. Five of 19 cells which were examined and labeled with biocytin showed long-term potentiation (LTP) of the EPSP, and 12 cells showed post-tetanic potentiation (PTP) following the tetanic stimulation. All the examined cells were pyramidal neurons. These results demonstrate that plasticity exists within the intracortical connection of the motor cortex that may be involved in motor learning.

Animals↗

Cerebellar and mesencephalic influence on bulbar penicillin-G epileptogenesis in rats.

The influence of the cerebellum and mesencephalon on epileptic bulbar discharge induced by topical application of penicillin-G on the floor of the IVth ventricle was analyzed in rats. Bulbar multiunit activity was recorded at different depths. The animals were divided into two main groups: totally cerebellectomized rats (Group I) and lobus anterior cerebellectomized rats (Group II). Each main group was further subdivided into two subgroups: animals with intact mesencephalon and animals with transected mesencephalon. In Group I: the total cerebellectomy, in intact mesencephalic rats (first subgroup) induced a sudden disappearance of bulbar epileptic discharge. The mid-collicular transection (second subgroup) produced the immediate disappearance of bulbar paroxysms and the total cerebellectomy, subsequently performed, further decreased the spontaneous firing rate. In Group II: (first subgroup) the lobus anterior ablation in rats with intact mesencephalon, significantly enhanced the paroxysmal discharge. In the second subgroup, where the midcollicular transection had provoked the disappearance of bulbar paroxysms, the lobus anterior ablation induced the immediate reappearance of the paroxysmal activity. The penicillin-G epileptogenic activity showed a different intensity at different depths in the bulb with a maximum intensity at the level of the vestibular nuclei. In conclusion, the present study shows that both the mesencephalon and the cerebellum have a facilitating influence on bulbar epileptic discharge induced by the topical application of the GABA antagonist. However, not all the cerebellum has a facilitating effect, because the anterior lobus was found to have an inhibitory influence on bulbar discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Visual and vestibular projections to tongue motoneurons.

The rabbit hypoglossal neurons, localized in the mediocaudal part of the XIIth nucleus, receive visual and vestibular inputs able to induce reflex responses functionally driven both to prepare the oral cavity for food reception and to ensure a correct postural arrangement of the tongue. The aim of the present research was to show a possible convergence of visual input on the hypoglossal neurons modulated by the vestibular system and, thus, demonstrate that visual input plays a part in the control of the tongue posture. It was found that 78% of tested neurons responded to both photic stimulation of the retinae, performed by a conventional strobe unit, and electrical stimulation of the labyrinth, with different patterns of response. Moreover, visual input significantly modified both the hypoglossal neuron response and the electromyographic genioglossal response to caloric stimulation of the labyrinth. Because a significant visual influence on the hypoglossal nucleus response and the genioglossal muscle response to labyrinthine stimulation was observed, it can be concluded that vision does integrate the spatial information of the labyrinth to modulate the postural tone of the tongue muscles.

Animals↗

The brainstem cardioarrhythmogenic triggers and their possible role in sudden epileptic death.

The cardiovascular effects of simultaneous activation of hypothalamic and mesencephalic cardioarrhythmogenic triggers were studied in hemispherectomized rats. Paroxysmal activity of hypothalamic neurons (HEF), elicited by topical application of penicillin G on the thalamus, triggered short-lasting bradyarrhythmic episodes, up to a maximum of 6 s, and alterations in repolarization. In the hypothalamic neurons, an additional penicillin G epileptic focus at mesencephalic level (MEF) induced the enhancement of paroxysmal activity by a recruitment of new units and potentiation of their background activity. HEF+MEF triggered second-degree 2:1-8:1 atrioventricular (A-V) blocks, impairment of the A-V conduction, alterations in the recovery phase and bundle branch blocks. After HEF, the arterial blood pressure decreased by 4-6%. HEF+MEF induced a further reduction of 17% in systolic pressure only. It is possible that the enhancement of the HEF following MEF could depend on MEF spreading upward. The HEF, in turn, by spreading downward could influence the MEF and so activate, between HEF and MEF, a circuitry with reciprocal co-excitation that could explain the more serious cardiovascular alterations observed during HEF+MEF compared with those observed during HEF only or during MEF only. However, this cardiovascular impairment, which must be neurogenic in origin as it was observed in animals with normal acid-base and blood parameter values, did not induce heart death. Thus, additional concomitances must be considered, such as metabolic derangement which can occur during seizures, to explain sudden death in epileptic patients. Some aspects of metabolic complications in cardiac activity during epilepsy are also discussed.

Acid-Base Equilibrium↗

Vestibular projections to hypothalamic supraoptic and paraventricular nuclei.

The effects of electrical stimulation of the eighth nerve and caloric stimulation of the labyrinth were tested on the spontaneous or evoked electrical activity of single neurons located in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. It was found that these neurons responded to both kinds of stimulation. In particular, the neurons of the SON showed a predominant response pattern characterized by a sequence of excitation-inhibition, whereas the neurons of the PVN showed different patterns of response with various combinations of inhibition and excitation sequences. The latencies of these neuronal responses to the electrically induced eight nerve volleys were compatible only with a polysynaptic connection. The possible pathways involved in this vestibulo-hypothalamic relation as well as their functional role are discussed.

Animals↗

Olfactory modulation of hypoglossal neuron activity.

Amyl acetate stimulation of the neuroepithelial cells of the olfactory mucosa induced significant responses in the olfactory bulb and modulated the spontaneous electrical activity of the hypoglossal neurons localized in the mediocaudal part of the XIIth nucleus. Olfactory stimulation induced several patterns of responses characterized by excitation, inhibition and combined effects frequently dependent upon the stimulation intensity. In addition, olfactory inputs converge with the visual inputs on the same part of the XIIth nucleus. The olfactory inputs inducing hypoglossal excitatory responses increased the hypoglossal excitation produced by visual stimuli and decreased its inhibition. Viceversa, the olfactory inputs inducing hypoglossal inhibitory responses decreased excitation and increased hypoglossal inhibition to photic stimulation of the retinae. The possible pathways involved in carrying the olfactory inputs towards the hypoglossal nucleus, and the olfactory or non-olfactory origin of the hypoglossal responses were considered. With regard to the role played by this input in the economy of the hypoglossal function, it was concluded that olfactory inputs, alone or together with visual inputs, may induce tongue reflex adjustments associated with the oral phase of digestion to prepare the oral cavity for food reception.

Animals↗

Visual and somatosensory information to tongue motoneurons.

The experiments were designed to show whether visual inputs and somatosensory signals travelling along the common radial nerves converge onto the same hypoglossal neurons. The hypoglossal neurons (HN) type I (45.77%) and II (33.89%) responded to both visual and somatosensory stimuli. The HN type III (15.26%) responded only to the retinae and type IV (5.08%) only to the forelimb nerves stimulation. In the convergent neurons, types I and II, the influence of the somatosensory stimulation on the hypoglossal visual response was also analyzed. The conditioning stimulation of the radial nerve significantly increased (31%) the hypoglossal response to the less effective retina and significantly reduced (17%) the response to the more effective retina. The recordings of the electromyographic activity of the genioglossus (GM) and the superior longitudinal muscle (SLM), showed that the somatosensory afferents synergize the excitatory effect of the visual messages on the extrinsic tongue muscles (GM) and antagonize the inhibitory effect that visual messages induce on the intrinsic tongue muscles (SLM). The results suggest that visual messages induce tongue reflex responses functionally directed not only to prepare the oral cavity better for food reception, as previously demonstrated, but also to modulate the postural tone of the tongue together with somatosensory signals.

Animals↗

Propofol anticonvulsant activity in experimental epileptic status.

We have examined the anticonvulsant properties of propofol in high doses in two experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)-induced seizures and partial, cortically applied penicillin G-induced seizures. Propofol was administered either as a single bolus injection or as a bolus injection followed by an infusion for 1 h. When administered as a single bolus injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the reappearance of electrical and clinical signs. In focal epileptic status, the single dose stopped paroxysmal activity and the associated clonic jerks for a few seconds. When the bolus dose was followed by an infusion, the firing bursts were replaced by isolated spikes, and contralateral jerks became sporadic and feeble. The greater efficacy of propofol against PTZ convulsions may be a reflection of the opposite action of the two drugs on neural membrane conductance: PTZ induces paroxysmal neural discharge by enhancing membrane conductance while propofol appears to decrease membrane conductance, thus suppressing paroxysmal discharge. There was no close relationship between blood concentration of the anaesthetic and its clinical effects, at least after a short-term infusion, as used in the present experiments. We suggest that propofol may be a potentially useful drug in status epilepticus in patients in whom benzodiazepines, barbiturates and phenytoin have failed.

Action Potentials↗

Alcohol withdrawal in rats is associated with a marked fall in extraneuronal dopamine.

Withdrawal of rats from chronic ethanol (2-5 g/kg, every 6 hr for 6 days) resulted in withdrawal symptomatology and dramatic fall in extracellular dopamine (DA) in the ventral striatum as measured by microdialysis. The changes in DA output paralleled the withdrawal symptomatology and both phenomena were reversed by a challenge ethanol dose (5 g/kg orally). The results suggest that the decrease in DA output may be responsible for the aversive symptoms of withdrawal.

3,4-Dihydroxyphenylacetic Acid↗

Metadoxine (pyrrolidone carboxylate of pyridoxine) antagonizes the locomotor-stimulatory effect of ethanol in mice.

The effects of metadoxine (pyrrolidone-carboxylic acid; PCA) and pyridoxine on the locomotor responses to ethanol in mice were compared. Metadoxine (200 and 400 mg/kg i.p.) and PCA (86 and 172 mg/kg) prevented, in a dose-related manner, the locomotor stimulant effect of a low dose of ethanol (1.5 g/kg i.p.), whereas pyridoxine (228 mg/kg i.p.) was completely ineffective. Neither compound modified the sedative effect of a high ethanol dose (2.5 g/kg i.p.). The results indicate that the antagonistic effect of metadoxine on ethanol stimulant response is due to the PCA component of the molecule.

Animals↗

Penicillin-induced paroxysmal activity in brainstem neurons.

The spontaneous electrical activity of single mesencephalic and bulbar neurons was recorded in hemispherectomized rats, following topical application of the GABA-antagonist penicillin-G on the mesencephalon or on the rhombencephalon, to investigate whether these structures could develop a specific penicillin paroxysmal activity independently of the upper structures. Twenty minutes following penicillin-G, the mesencephalic neurons developed paroxysmal activity characterized by a significant increase in the spontaneous electrical activity, the appearance of multiunit activity and, frequently, phasic activity with rhythmical outbursts. The paroxysmal activity at bulbar level appeared later than that observed in the mesencephalon and was characterized by a significant increase of the spontaneous firing rate of the neurons, single short bursts and sometimes rhythmical outbursts. The bulbar outbursts always discharged at lower frequency than those at the mesencephalic level. Following a midcollicular transection the paroxysmal bulbar activity abruptly disappeared. This phenomenon might be explained by a loss of facilitation from superior structures on the bulbar neurons which in roditors show a poor GABA-receptor distribution. In other words, penicillin alone, due to the scarcity of GABA receptors, might not be sufficient to induce paroxysmal activity in bulbar neurons but the simultaneous presence of both the superior facilitation and the drug might enhance neuronal excitability to a critical level. However, the diffusion of the drug upwards to the mesencephalon, with consequent activation of a system allowing the downward propagation of paroxysmal activity, cannot be excluded. In conclusion, while the mesencephalic neurons demonstrate a proper ability to develop penicillin paroxysmal discharge, the bulbar neurons must be sustained by intact connections with upper structures to be able to do so.

Animals↗

Interaction of 1-methyl-4-phenylpyridinium ion and tyramine with a site putatively involved in the striatal vesicular release of dopamine.

The neurotoxin MPP+ potently inhibited the striatal binding of [3H]-tyramine, a putative marker for the vesicular transporter of dopamine, and provoked a massive in vivo release of striatal dopamine. Tetrabenazine, an established ligand for the vesicular catecholamine carrier, potently inhibited [3H]-tyramine binding, tyramine-provoked striatal efflux of dopamine and the fast component of MPP(+)-induced dopamine release. It is concluded that MPP+ in the striatum, besides interacting with additional intracellular targets, avidly binds at a vesicular site functionally involved with the outward transport of dopamine.

Animals↗