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E Merlo Pich

Publications and source records attributed to E Merlo Pich.

13 recordsLinked to original sources

Intramembrane interactions between neurotensin receptors and dopamine D2 receptors as a major mechanism for the neuroleptic-like action of neurotensin.

Evidence has been presented that behavioral actions of NT, inducing its neuroleptic-like action, can be explained on the basis of NT-D2 intramembrane receptor-receptor interactions in the basal ganglia, unrelated to the coexistence phenomenon, leading to reduced affinity and transduction of the D2 agonist binding site. By reducing selectively D2 receptor transduction at the pre- and postsynaptic level, the NT receptor appears capable of switching the DA synapses towards a D1 receptor-mediated transduction, illustrating how receptor-receptor interactions can increase the functional plasticity of central synapses (FIG. 12).

Animals

Siagoside selectively attenuates morphological and functional striatal impairments induced by transient forebrain ischemia in rats.

BACKGROUND AND PURPOSE: Transient forebrain ischemia induced in rats by the four-vessel occlusion method is known to produce severe neural damage in the hippocampus and striatum and a behavioral syndrome the major symptom of which is a working memory deficit. Recent evidence suggests that monosialogangliosides can ameliorate postischemic symptoms. Our purpose was to study the effect of siagoside, the inner ester of GM1 ganglioside, on some behavioral and morphological impairments induced by four-vessel occlusion in rats. METHODS: Rats were injected daily with 5 mg/kg i.p. siagoside starting 4 hours after the cerebral ischemia. After 14 days the rats were tested for working memory in a water T maze or scored for apomorphine-induced stereotypy. The rats were killed 21 days after the cerebral ischemia. Histological and computer-assisted morphometric analyses were performed on cresyl violet-stained brain sections, which were graded according to a neuropathologic score, and on sections stained with a monoclonal antiserum against dopamine and cyclic adenosine-3',5'-monophosphate-regulated phosphoprotein, a marker for striatal dopaminoceptive neurons. RESULTS: Siagoside treatment reduced the stereotypy score induced by low doses of apomorphine and the extent of striatal lesions but did not affect the working memory deficit or the extent of hippocampal lesions. CONCLUSION: Daily siagoside treatment after acute cerebral ischemia attenuates some morphological and functional deficits related to striatal damage. These effects can be interpreted as a selective protective action on striatal neural populations or as a modulatory action on neural systems involved in striatal control. These data are consistent with preliminary clinical reports showing that monosialogangliosides enhance motor recovery after acute ischemic stroke.

Animals

Effects of indole-pyruvic acid on sleep and food intake in the rat.

Indole-pyruvic acid was studied for its short- and long-term effects on electroencephalographic sleep and on food intake in rats implanted with cortical and muscular electrodes. Following a single injection, indole-pyruvic acid (10-50 mg kg-1 i.p.) reduced by 16-23 min (range) the latency of the first slow-wave episode in a dose-related fashion and produced a significant increase in slow-wave sleep time (12-40%) in doses of 10-30 mg kg-1. Rapid eye movement sleep latency and rapid eye movement sleep time were increased (by 23-37 min) and reduced (57-71%) respectively. The effects of indole-pyruvic acid on slow-wave sleep time were still present after 3, 7 and 14 days of chronic administration (10 mg kg-1 day-1), whereas tolerance to the effect of indole-pyruvic acid on rapid eye movement sleep was observed. Daily food consumption was reduced (20-28%) by acute administration of indole-pyruvic acid (15-30 mg kg-1 i.p.), but tolerance developed after 5 days of repeated injections. These findings are in accordance with previous evidence suggesting that indole-pyruvic acid effects may be related to the activation of central serotonin neurons, which are involved in the inhibitory control of sleep and food intake.

Animals

On the role of neuropeptide Y in information handling in the central nervous system in normal and physiopathological states. Focus on volume transmission and neuropeptide Y/alpha 2 receptor interactions.

The NPY neurons play an important role in information handling in the CNS by their ability to interact in both wiring and volume transmission at the network, local circuit and synaptic level. The importance of NPY/alpha 2 receptor-receptor interactions in cardiovascular, neuroendocrine and vigilance control is emphasized. Alterations in these receptor-receptor interactions take place in the spontaneously hypertensive rats as well as in the ischemic brain, which may have profound consequences for the information handling and contribute to the functional alterations found in these pathophysiological states. Finally, in the aging brain there appears to exist a marked reduction in NPY transmission line, which may affect higher brain functions, such as learning and memory retrieval. The most impressive result is, however, the indications of a role for NPY in volume transmission, where NPY appears to produce syndromic actions via its conversion into biologically active fragments, which may have preferential actions at Y2 NPY receptors. These syndromic pathways may be altered in the spontaneously hypertensive rat and may be controlled by gonadal steroids and glucocorticoids. Glucocorticoid receptors have been demonstrated in all arcuate NPY neurons and all NA/NPY and A/NPY costoring neurons.

Aging

Morphometrical and microdensitometrical studies on phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive nerve terminals and on glucocorticoid receptor-immunoreactive nerve cell nuclei in the paraventricular hypothalamic nucleus in adult and old male rats.

The phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive nerve terminal profiles and the glucocorticoid receptor-immunoreactive nuclear profiles have been characterized in the parvocellular part of the paraventricular hypothalamic nucleus of the adult (3 month) and the old (24 month) male rat. The phenylethanolamine-N-methyltransferase-, neuropeptide Y- and glucocorticoid receptor-immunoreactive structures have been demonstrated by means of the indirect immunoperoxidase procedure and analysed in a quantitative way by means of morphometrical and microdensitometrical approaches using both semiautomatic and automatic image analysis. During aging there is (a) a marked reduction in the number of neuropeptide Y-immunoreactive profiles, a moderate reduction of phenylethanolamine-N-methyltransferase-immunoreactive profiles and a small reduction in the number of glucocorticoid receptor-immunoreactive profiles without a significant change in the evenness of distribution of such profiles as evaluated by means of Gini's index; (b) a loss of the significant correlation in the distribution of the glucocorticoid receptor- and phenylethanolamine-N-methyltransferase-immunoreactive profiles at the two most caudal levels analysed (A5150 and A5270 micron) while a significant correlation developed between these two distributions at a more rostral level (A5400 micron); (c) a substantial decline in the overlap area of the glucocorticoid receptor- and phenylethanolamine-N-methyltransferase-immunoreactive profiles at four out of five rostrocaudal levels analysed; (d) a marked reduction in the density-intensity of the neuropeptide Y-immunoreactive profiles and a small significant reduction in the density-intensity of the phenylethanolamine-N-methyltransferase-immunoreactive profiles without any associated changes in the intensity of the glucocorticoid receptor-immunoreactive profiles. Furthermore, three-dimensional reconstructions of the overall distribution of the glucocorticoid receptor-, phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive structures have been made in the paraventricular hypothalamic nucleus of the adult male rat. The present results indicate a reduction of neuropeptide Y- and phenylethanolamine-N-methyltransferase-immunoreactive nerve terminal profiles in the parvocellular part of the paraventricular hypothalamic nucleus during aging. These results may in part reflect a loss of neuropeptide Y-like peptides in phenylethanolamine-N-methyltransferase-immunoreactive nerve terminals of the paraventricular hypothalamic nucleus, favouring our view that during aging the modulatory peptides may be lost, leading to a loss of

Aging

Chronic uridine treatment reduces the level of [3H]spiperone-labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine-dependent behaviours.

The effect was studied of chronic uridine treatment on the recovery of striatal D-2 dopamine (DA) receptors after their irreversible blockade by N-ethoxycarbonyl-2-ethoxy-I,2-dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [3H]spiperone as radioligand. Chronic uridine treatment (15 mg kg-1 day-1, i.p., 14 days) causes a reduction of [3H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [3H]spiperone-labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDQ-induced syndrome is more rapid in the young rats treated with uridine than in the saline-treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D-2 DA receptors.

Adrenergic alpha-Antagonists

Evidence for a fast receptor turnover of D1 dopamine receptors in various forebrain regions of the rat.

The time course for recovery of binding of the D1 dopamine receptor antagonist radioligand [3H]SCH 23390, after administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), was studied in the neostriatum, nucleus accumbens, tuberculum olfactorium and claustrum of the rat by means of quantitative receptor autoradiography. The results showed that the receptor degradation rate constant (k) ranged from 0.0163 to 0.0315 h-1 and that the receptor production rate (r) ranged from 8.52 to 24.96 fmol/mg protein/h. These results indicate that the D1 receptor has a considerably faster turnover than the D2 receptor, which suggests that the D1 receptor may require a dynamic regulation including also changes in receptor production and degradation rates.

Animals

Long-term prognosis after carotid endarterectomy.

This study analyzed 76 consecutive patients with carotid transient ischemic attacks (TIA) and carotid lesions appropriate to symptoms who underwent endarterectomy during the period 1975-1981. The mean age of the patients was 51.9 +/- 8 years at the time of surgery. Hypertension was present in 32.9%, diabetes mellitus in 13%, ischemic cardiopathy in 8.2% and peripheral vascular disease in 6.6%. Operative mortality was 1.3% and harder morbidity 4%. The average follow-up was 2.6 years (range 1-7 years). The observed 5-year survival rate was 85.2% compared to the expected rate of 92.4% in a normal population. During the follow-up 5 patients had a stroke: the cumulative stroke rate was 4.6% at 1 year and 7.9% at 3 years. 18 patients had further TIAs (13 carotid TIAs and 5 vertebro-basilar TIAs). 6 patients suffered myocardial infarction. The prognosis of TIA patients treated with endarterectomy is difficult to evaluate because the natural history of TIAs is still undefined.

Actuarial Analysis

Actions of centrally administered neuropeptide Y on EEG activity in different rat strains and in different phases of their circadian cycle.

The effects of centrally administered neuropeptide Y (NPY) on the sleep-wakefulness cycle have been studied by analyzing its action in different strains of rats with or without spontaneous hypertension and during two different phases of the circadian cycle. Normal adult Sprague-Dawley (SD), Wistar-Kyoto (WKy) and spontaneous hypertensive (SH) rats were used. By means of EEG electrodes the recording of the fronto-parietal electrocorticogram and the electromyogram could be made. Stainless steel cannula were also implanted into the lateral ventricle. The effects of an intraventricular injection of NPY (1.25 nmol/rat) was compared with the effects of the vehicle (saline) alone. The EEG patterns were classified as desynchronized, mixed or synchronized. In the SD rats NPY produced behavioural signs of sedation and a significant reduction of synchronized EEG activity as well as significant increase of synchronized and mixed EEG activities in comparison with the saline treated rats. In the WKy rats NPY administration produced an increase of synchronized EEG activity during evening sessions. In SH rats NPY produced a significant increase of desynchronized EEG activity and a decrease in mixed EEG activity indicating an awakening effect of the peptide. In view of the NPY innervation of the locus ceruleus, it therefore seems possible that the neuronal and hormonal regulation of the locus ceruleus noradrenaline nerve cells is different in the two strains of rats. It also seems possible that the ability of NPY to increase wakefulness in hypertensive animals is related to abnormal changes in the alpha 2-adrenoreceptors taking place in SH rats.

Animals

Studies on aging processes.

By means of computer assisted morphometry and microdensitometry it has been possible to characterize aging processes in transmitter identified neurons demonstrated at the presynaptic level by immunocytochemistry and at the postsynaptic level by receptor autoradiography. Three-month- and 24-month-old rats were used in the present study. It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact. In this quantitative receptor autoradiographical analysis 3H-spiperone and 3H-N-propyl-norapomorphine were used as radioligands for DA receptors. In comparison with the aging induced changes in DA receptors in the striatum and in the nucleus accumbens the alpha 2- and the beta-adrenergic receptors appeared to be more resistant to the aging process. In the analysis of the opiate receptors of the aging brain it could be demonstrated by quantitative receptor autoradiography using both radioligands for the mu-type (3H-etorphin) and delta-type (3H-d-ala2-d-leu5-enkephalin) of opiate receptors that there is a marked and widespread disappearance of both types of opiate receptors in the aging brain. It must be emphasized that no correlation exists in the degeneration pattern of the mu- and delta-type of opioid receptors indicating that they may represent two separate entities with separate trophic regulation. In contrast, it was discovered in the quantitative receptor autoradiographical analysis that 3H-flunitrazepam binding was increased in many areas of the aging brain compared with the adult rat brain. These results underline the heterogeneity in the degenerative patterns which take place in transmitter receptors in relation to aging. Thus, these results indicate that the simple replacement therapy in aged patients may not give optimal results. As a matter of fact, such treatments can lead to a further unbalance between the various types of transmitter identified neurons building up the neuronal networks of the brain, which are undergoing degeneration.

Aging

A two-compartment exploratory model to study anxiolytic/anxiogenic effects of drugs in the rat.

The response of a recently described light/dark choice novelty situation to anxiolytic and non-anxiolytic agents as well as to putative anxiogenic drugs was assessed in rats. Diazepam (1.0-10.0 mg/kg, i.p.), chlordiazepoxide (2.5-10.0 mg/kg, i.p.), and pentobarbital (pentobarbitone) (7.5-15.0 mg/kg, i.p.) enhanced rats' activity in the dark and brightly lit compartments as well as crossings between the two, while imipramine (5-20 mg/kg, i.p.) had no effects. None of these drugs changed animal locomotion in activity cages. d-Amphetamine (1.5 mg/kg, i.p.) caused a significant increase in the three parameters used to measure rats' exploratory activity, but the effect was due to an increase in the general activity of the animal. No tolerance to the effects of diazepam developed after daily treatment with 5 mg/kg i.p. for 15 days. Non-sedative and non-convulsant doses of putative anxiogenic drugs such as yohimbine (2.5-5.0 mg/kg, i.p.), picrotoxin (2.0-4.0 mg/ml, i.p.) and ethyl-beta-carboline-3-carboxylate (2.5-5 mg/kg, i.p.) reduced the exploratory activity of rats in the dark compartment. The advantages and problems of using this test to identify anxiolytic and anxiogenic drugs are discussed.

Animals