Biomedical subjects

D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 91 records · Page 5Linked to original sources

PubMed1994

Increased pineal melatonin content coupled to restricted water availability in a Pavlovian conditioning paradigm in rats.

The objective of this study was to assess whether rat pineal melatonin content could be modified in a classical conditioning paradigm. In rats kept under light (200 lux) from 06.00 to 18.00 h daily, the time of lights off was selected as the unconditioned stimulus (US). Restricted water availability (from 10 min before to 10 min after light-dark, LD, transition) was the conditioned stimulus (CS). The conditioned and unconditioned responses were measured as the changes in pineal melatonin levels 4 h after LD transition. In animals under regular lighting conditions, lights out at 18.00 h (the US) caused a 4.4-7.8-fold increase of pineal melatonin concentration 4 h after later, when compared to animals maintained under light for the 4 h-period. After a training period of 7 days of restricted water availability (the CS), significantly augmented pineal melatonin levels were found in rats that were exposed to water but were maintained under light for the 4 h period after expected LD transition. The control animals for this experiment, i.e., rats which had undergone the training period, were kept for 4 h under light after expected LD transition, and did not receive water at LD transition, exhibited very low pineal melatonin levels. The conditioned increase of pineal melatonin content attained lower values than those in rats exposed to normal lighting conditions. It also fulfilled the contingency criterion, that is, it caused at trial a significant elevation of pineal melatonin content only when water availability was applied from 10 min previously to LD transition during training, and not 20 min after LD transition. After a training period of 7 days, restricted water availability applied 4 h before lights off (at 14.00 h), caused an enhanced production of melatonin 4 h later, regardless of the animals being exposed either to a dark or to a light environment. The results indicate that pineal melatonin production can be manipulated in a classical conditioning paradigm, when an appropriate CS stimulus is used.

Animals↗

PubMed1994

Peripheral autonomic regulation of gonadotropin secretion in pubertal rats. Inhibition of post-castration rise of gonadotropins during wallerian degeneration after sympathetic superior cervical ganglionectomy.

Shortly after superior cervical ganglionectomy (SCGx) peripheral sympathetic nerve terminals in the median eminence degenerate, the neurotransmitter is released, and a transient period of increased postsynaptic ensues. The present experiments were undertaken to examine, in the anterograde degeneration paradigm after SCGx, the participation of peripheral sympathetic nerves in feedback regulation of gonadotropin release in pubertal rats. Groups of 18 days old or 26 days old rats of both sexes were subjected to castration or its sham-operation, and 4 h later to SCGx or sham-SCGx. Twenty-four h later, the rats were decapitated and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured by RIA. In 19 days old male rats, the post-castration increase of circulating LH, but not of FSH, was prevented by the wallerian degeneration of sympathetic nerves after acute SCGx. At the 27th day of life, acute SCGx prevented FSH, but not LH, post-orchidectomy rise. In female rats, SCGx blunted the oophorectomy-induced increase of gonadotropin levels at both examined ages. SCGx brought about a significant decrease of serum LH levels in 19 days old, sham-castrated female rats. At the 19th day of life, acute SCGx decreased serum LH and FSH in neonatally orchidectomized rats, but not in neonatally androgenized female rats. The data are in favor of a negative influence of peripheral sympathetic neurons on gonadotropin release in prepubertal rats, predominantly in female rats.

Age Factors↗

PubMed1994

Parasympathetic control of parathyroid hormone and calcitonin secretion in rats.

Cholinergic nerve fibers can be traced to the vicinity of C- and parathyroid cells. The objective of this study was to examine the changes in circulating calcium, parathyroid hormone (PTH) and calcitonin levels after a bilateral surgical section of thyroid (TN) or inferior laryngeal nerves (ILN) in rats. Parasympathetic surgical section decreased significantly thyroid and parathyroid neuronal [3H]choline uptake. A significant fall in total serum calcium and a significant increase in serum PTH were observed 10 days after TN and ILN sections, while calcitonin levels decreased significantly after ILN sections only. When parathyroid sensitivity to a hypocalcemic challenge was assessed, a significantly larger serum PTH response to EDTA was detectable in TN- or ILN-sectioned rats. A significantly smaller hypocalcemia after EDTA was observed in TN-sectioned rats only. Following calcium chloride injection, the increase in serum calcitonin was greater, and the increase in serum calcium levels smaller, in TN-sectioned rats as compared to sham-operated controls. In ILN-sectioned rats, the secretory response of calcitonin and the hypercalcemia achieved after a calcium chloride challenge was significantly greater than in controls. The results indicate that ILN or TN sections induced hypocalcemia and increased serum PTH levels in rats, as well as bringing about a greater secretory response of PTH and calcitonin when challenged with an appropriate stimulus. An inhibitory parasympathetic influence parathyroid and C-cell secretion can be envisioned.

Animals↗

PubMed1994

Pharmacological profile and diurnal rhythmicity of 2-[125I]-iodomelatonin binding sites in murine mammary tissue.

Recent studies demonstrated that melatonin treatment decreased the growth of mammary glands in pubertal and pregnant mice. In vitro, melatonin inhibited murine mammary gland growth at microM concentrations and increased it at pM concentrations. Melatonin-induced changes of cyclic nucleotide synthesis was also demonstrated in mammary gland slices in vitro. The objective of the present study was to assess the possible existence of specific binding sites for melatonin in murine mammary gland by using 2-[125I]-iodomelatonin as a probe. The specific binding of 2-[125I]-iodomelatonin to murine mammary gland membranes was rapid, saturable, and reversible, showed an affinity in the low nM range, and displayed time, temperature, and pH dependence. Scatchard analysis indicated the existence of a single class of binding sites that exhibited a diurnal rhythmicity in affinity (Kd) and receptor density (Bmax). A maximum in Bmax (267 +/- 42 fmol/mg protein) was found at the light period, while affinity was maximal during darkness (Kd = 1.33 +/- 0.22 nM). In competition studies dopamine and dopamine-related agents, as well as 6-hydroxymelatonin and serotonin, but not melatonin, effectively displaced 2-[125I]-iodomelatonin from mammary binding sites. The results demonstrated a specific binding of 2-[125I]-iodomelatonin to murine mammary glands, with affinity in the low nM range, and a pharmacological profile that differed from that reported for 2-[125I]-iodomelatonin acceptor sites in other tissues.

Animals↗

PubMed1994

Peripheral neuroendocrinology of the cervical autonomic nervous system.

1. The sympathetic superior cervical ganglia (SCG) provide innervation to the pineal gland and median eminence through the internal carotid nerve and to the thyroid and parathyroid glands through the external carotid nerve. 2. Postsynaptic activation in median eminence nerve endings shortly after superior cervical ganglionectomy (SCGx) was accompanied by a depression of LH and FSH release and by a 3-5 day delay in rat estrous cyclicity. A decrease in TSH and GH release and an increase in ACTH and prolactin release were also found. These effects were accompanied by a) an increase in medial basal hypothalamic (MBH) LHRH, TRH and GHRH, b) a decrease in MBH somatostatin, AVP and CRH, and c) a normal adenohypophyseal response to hypophysiotropic hormones. Neurohypophyseal AVP release decreased during degeneration of sympathetic nerve terminals in the neurohypophyseal lobe after SCGx. The effects were generally mediated by alpha 1-adrenoceptors and were pineal gland. 3. In thyroid and parathyroid tissue the following events were observed during the wallerian degeneration phase after SCGx: a) alpha 1-adrenoceptor inhibition of thyroxine (T4) release, b) alpha 1-adrenoceptor inhibition, together with beta-adrenoceptor stimulation, of calcitonin release, and c) alpha 1-adrenoceptor inhibition of parathyroid hormone release. Thyroid sympathetic nerves also modulate slow phenomena such as compensatory thyroid growth after partial thyroidectomy. 4. In rats subjected to cholinergic decentralization of the thyroid gland, a decrease of plasma T4 and an increase of plasma TSH, as well as an impaired goitrogenic and thyroid compensatory response were detectable. The calcitonin and PTH response to changes in calcium levels increased after regional parasympathetic denervation. 5. The results indicate that cervical autonomic nerves constitute a parallel pathway through which the brain communicates with the endocrine system.

Animals↗

PubMed1993

Melatonin as an anxiolytic in rats: time dependence and interaction with the central GABAergic system.

Anxiolytic and pro-exploratory melatonin properties were assessed in rats using a plus-maze procedure. Both melatonin (1 mg/kg) and diazepam (0.5 mg/kg) showed a significant diurnal variation to decrease anxiety and to promote exploratory behavior. Melatonin displayed anxiolytic activity at night, with absence of effects at noon and a weak activity at the beginning of the light phase. Melatonin pro-exploratory activity was found only at night. Diazepam exerted significant anxiolysis during the night, with less activity during the day. Diazepam pro-exploratory activity was found during the night only. A dose-response study carried out by injecting 1-20 mg/kg melatonin at 12:00 or 18:00 h indicated that melatonin activity was greatest at 18:00 h. Diazepam was anxiolytic at both times, and pro-exploratory at 18:00 h only. Melatonin activity was blunted by administration of the benzodiazepine antagonist, flumazenil.

Analysis of Variance↗

PubMed1993

Wheel running raises body temperature and changes the daily cycle in golden hamsters.

The purpose of this study was to characterize the influence of wheel-running activity on temperature circadian rhythm in golden hamsters. Amplitude of body temperature rhythm was significantly higher in animals that had access to the running wheel. Qualitatively, wheel running resulted in squaring of temperature rhythm waveform, a phenomenon that was independent of ambient illumination. When the hamsters had access to an immobilized wheel, the effect on temperature was no longer observed. Fast Fourier Transformation after subtracting 24-h sine waveforms (to rule out harmonics of the principal frequency), indicated distinct secondary components of the rhythms, i.e., a 12-h component in animals that had access to the wheels and an 8-h component in animals that did not. The rise in body temperature could be dissociated from the start of the activity period, body temperature augmenting before the time of light-dark transition, while activity increased about 12 min later. On the first night after presentation of an estrous female, the temperature cycle in male hamsters that did not access to the wheels was similar to that found in animals running on the wheels; the effect was no longer observed in subsequent nights. The results contribute to the view that the spontaneous locomotor activity in hamsters has a significant effect on temperature cycle.

Animals↗

PubMed1993

Diurnal changes of GABA turnover rate in brain and pineal gland of Syrian hamsters.

Circadian rhythms of GABA turnover rate in cerebral cortex, preoptic area-medial basal hypothalamus (PMBH), cerebellum, and pineal gland were examined in Syrian hamsters kept for 3 months under either long (14 h of light/day) or short days (10 h of light/day). In vivo GABA turnover rate was measured by the increase of GABA levels following inhibition of GABA-transaminase by gamma-acetylenic GABA. Under long photoperiods, a significant rhythm of GABA turnover was detected in the four areas studied (cerebral cortex, PMBH, cerebellum, and pineal gland), with maxima at night. A Cosinor analysis indicated acrophases which varied from 2300 to 0400 h (3rd to 8th h of darkness). Under short photoperiods, there were no significant circadian variations in GABA turnover in the cerebral cortex, and the synchronization in turnover rate among the remaining regions was lost, with acrophases being detectable either during the light phase of daily photoperiod (PMBH) or at night (cerebellum, pineal gland). Steady state levels of GABA also changed periodically in the same brain regions under both lighting environments, although phase relationships of circadian rhythms in GABA content and turnover rate varied significantly among tissues, as well as on photoperiodic conditions.

Animals↗

PubMed1993

Melatonin accelerates reentrainment after phase advance of the light-dark cycle in Syrian hamsters: antagonism by flumazenil.

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D-2, D-1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, approximately 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.

Analysis of Variance↗

PubMed1993

Involvement of the cervical sympathetic nervous system in the changes of calcium homeostasis during turpentine oil-induced stress in rats.

Hypocalcemia is a common finding during stress. The objective of this study was to examine: (a) the changes in circulating calcium, parathyroid hormone (PTH) and calcitonin (CT) concentration in rats stressed by being given a subcutaneous injection of turpentine oil, and (b) the involvement of the sympathetic cervical pathway in stress-induced changes of calcium homeostasis. Four hours after receiving turpentine oil or vehicle, rats were subjected either to hypocalcemia, by being given EDTA intraperitoneally, or to hypercalcemia, by being injected CaCl2 intraperitoneally. Significant changes in serum calcium (10% decrease), serum PTH (28% increase) and CT levels (40% decrease) were observed in stressed rats. EDTA administration brought about a significantly greater hypocalcemia, and a higher PTH secretory response in turpentine oil-stressed rats. During stress, the increase of serum calcium after CaCl2 was significantly smaller, and the rise of CT was greater than in controls. In the case of CT the changes were still observed in rats subjected to superior cervical ganglionectomy (SCGx) 14 days earlier. In the case of PTH, the increase found in stressed rats, but not the augmented response after EDTA, was blunted by SCGx. The potentiation of hypocalcemia brought about by turpentine oil was no longer observed in SCGx rats. In vehicle-treated controls, SCGx delayed PTH response to hypocalcemia, but did not affect the increased response of CT to CaCl2 challenge. The results indicate that a number of changes in calcium homeostasis arise during turpentine oil stress in rats. SCGx was effective to modify the set point for PTH release, but played a minor role in affecting the augmentation of CT release during stress.

Animals↗

PubMed1993

The effects of melatonin in human platelets.

Pineal melatonin has been implicated in the control of several physiological processes, including circadian rhythmicity and the photoperiodic control of seasonal breeding in mammals. However, its role in humans remains largely undefined. Presumably, melatonin acts on the CNS to affect biologic rhythms; additionally, a number of studies indicate the existence of direct effects of melatonin in peripheral organs, like the platelets. This article discusses experimental data indicating that the human platelets are peripheral cells sensitive to melatonin that could be potentially employed in clinic studies. Melatonin inhibits several physiological processes in platelets including the aggregation phenomenon the release of ATP and serotonin (indexes of the platelet secretory mechanism), and the production of thromboxane B2 A generally greater, and dose-dependent, effect of nanomolar melatonin concentrations in the evening as compared to morning melatonin found in vivo. The maximum in melatonin activity on platelet function precedes the peak in melatonin concentration in blood, indicating the existence of a dissociation between circulating levels and sensitivity to platelet the hormone in normal subjects. In binding studies employing 3H-melatonin as ligand, binding sites in human platelet membranes with a Kd within the nanomolar range were detected. The data suggest the feasibility to employ platelets as peripheral "windows" of central melatonin activity in humans.

Adenosine Triphosphate↗

PubMed1992

Time-dependent anticonvulsant activity of melatonin in hamsters.

The objective of the present study was to assess whether the anticonvulsant activity of melatonin displays diurnal variability in hamsters. Convulsions were induced by administering 3-mercaptopropionic acid (3-MP). There was a significant diurnal variation in 3-MP-induced convulsions, hamsters being more prone to exhibit seizures during the night than during the day. Melatonin (50 mg/kg i.p.) had a maximal anticonvulsive effect in the early evening (20:00 h). The administration at 20:00 h of the central-type benzodiazepine antagonist, Ro 15-1788, although unable by itself to modify seizure threshold, blunted the anticonvulsant response to melatonin. The results indicate that the time-dependent anticonvulsant activity of melatonin is sensitive to central-type benzodiazepine antagonism.

3-Mercaptopropionic Acid↗

PubMed1992

Neurochemical evidence for a neuronal GABAergic system in the rat sympathetic superior cervical ganglion.

Some characteristics of gamma aminobutyric acid (GABA) uptake and release in rat superior cervical ganglion (SCG) were investigated. Kinetic analysis of GABA uptake indicated the existence of both high affinity (Km = 18.6 microM) and low affinity (Km = 485 microM) uptake systems. 3H-GABA influx was decreased by inhibitors of glial (beta-alanine), neuronal (2,4-diaminobutyric acid, DABA), or glial and neuronal GABA uptake (nipecotic acid). 3H-GABA efflux was elicited by K+ depolarization in a dose-dependent manner, an effect unaltered by severing the preganglionic nerve fibers. Superfusion of SCG explants with DABA or beta-alanine resulted in increased 3H-GABA efflux from tissue, an effect amplified by the absence of calcium in the superfusion medium. 3H-GABA loading in the presence of DABA, but not in the presence of beta-alanine, resulted in abolition of K(+)-elicited 3H release. At 20 mM, but not at 50 mM K+, the release of 3H-GABA was inhibited by replacing Ca2+ by Mg2+ and by adding EGTA, or by incubating SCG in the presence of the Ca(2+)-channel blocker verapamil. Veratrine evoked GABA release in Ca(2+)-independent manner. None of several putative SCG autacoids or agonists (nicotine, muscarine, norepinephrine, dopamine, serotonin, baclofen, muscimol) significantly modified GABA release.

Acetanilides↗

PubMed1992

Time-dependent anesthetic and anticonvulsant activities of alphaxalone in Syrian hamsters.

To assess whether the anesthetic and anticonvulsant activities of alphaxalone display diurnal variability, groups of Syrian hamsters were studied at 4 h-intervals during a 24 h-cycle. The administration of alphaxalone (5 mg/kg) brought about a greater anesthetic activity (loss of righting reflex) at the middle of the photophase. When assessed in hamsters injected with 3-mercaptopropionic acid, alphaxalone displayed maximal anticonvulsant activity at the 4th of darkness. Evaluation of the time needed for first convulsive response indicated that alphaxalone did not show time-dependent effects, while in control hamsters seizure threshold was low during daylight and attained maximal values at night, showing a peak in seizure threshold at light-dark transition.

3-Mercaptopropionic Acid↗

PubMed1992

Light exposure patterns in schizophrenia.

Spontaneous light exposure patterns were studied in 10 chronic schizophrenic patients. Half of our schizophrenic patients exposed themselves to bright light exceeding ordinary indoor illumination. There was a significant positive correlation between the percentage of exposure to bright light and the Brief Psychiatric Rating Scale subscore anergia and a significant negative correlation with depression.

Adult↗

PubMed1992

Binding sites for [3H]-melatonin in human platelets.

A number of in vitro effects of melatonin on human platelets were revealed in previous studies. In order to examine whether high affinity binding sites for [3H]-melatonin were present in membrane preparations of human platelets, a rapid filtration procedure through Whatman GFB paper was employed. Maximal melatonin binding was attained within 3 hr at 0 degree C. Scatchard analysis indicated a single population of binding sites with a dissociation constant (Kd) = 4.1 +/- 0.5 nM and maximal number of binding sites (Bmax) = 24.2 +/- 1.9 fmol/mg protein (mean +/- SEM of five experiments). When various indole analogs were tested for their ability to inhibit [3H]-melatonin binding, the following Ki (nM) were obtained: 6-chloromelatonin (11.4), 2-iodomelatonin (22.0), melatonin (24.7), 5-methoxytryptophol (49.9), N-acetylserotonin (68.9), 6-hydroxymelatonin (78.2), 5-methoxytryptamine (184). Serotonin was a potent inhibitor of [3H]-melatonin binding with a Ki = 20.6 nM. Except for 2-methylserotonin and alpha-methylserotonin, a number of serotonin agonists and antagonists tested did not affect melatonin binding to platelet membranes. Binding experiments carried out at either 0800 or 2000 did not reveal time-dependent differences in Kd or Bmax. The results suggest that high affinity melatonin acceptors are present in human platelets.

Adult↗

PubMed1992

Diurnal changes in cyclic nucleotide response to pineal indoles in murine mammary glands.

The aim of this study was to determine whether pineal indoles affect cyclic nucleotide levels in mammary gland slices of BALB/c adult mice. Melatonin at 0.1 nM-10 microM concentrations decreased cAMP and augmented cGMP concentration in murine mammary gland slices in the presence of a phosphodiesterase inhibitor (1 mM theophylline), an index of cyclic nucleotide synthesis. Melatonin-induced changes in cyclic nucleotide levels were significantly larger at the end of the light period (2000) than in the morning (at 1000). Indole-induced inhibition of cyclic AMP levels by mammary slices exhibited the following order of potency: 5-methoxytryptamine > melatonin > or = 6-hydroxymelatonin > serotonin, N-acetylserotonin > 5-hydroxytryptophol. The order of potency for indole-induced augmentation of cyclic GMP levels was: 5-methoxytryptamine > melatonin > 6-hydroxymelatonin > serotonin, N-acetylserotonin, 5-hydroxytryptophol. When melatonin or 5-methoxytryptamine (10 nM) were examined for their effects on cAMP and cGMP levels in mammary glands of mice killed at six different time intervals during the 24-hr cycle, the activity was maximal during night. The data demonstrate that 5-methoxytryptamine and melatonin decreased cAMP and increased cGMP levels in mammary gland slices. Methoxyindole-induced changes in cyclic nucleotide synthesis in murine mammary glands exhibit the time-dependency known to occur in several other melatonin-influenced responses.

Animals↗

PubMed1992

Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism.

We endeavored to determine whether three behavioral effects of melatonin in rodents, i.e., depression of locomotor activity in hamsters, analgesia in mice, and impairment of 3-mercaptopropionic acid (3-MP) convulsions, exhibited the time dependency known to occur for several neuroendocrine effects of the hormone. Activity was monitored and registered by means of an optical actometer, and analgesia was assessed by the hot-plate procedure. Locomotor activity, analgesia, and seizure susceptibility were maximal at the beginning of the scotophase and minimal at noon. The effects of melatonin on the three parameters peaked at early night. The administration of the benzodiazepine antagonist flumazenil, although unable by itself to modify locomotor activity, pain, or seizure threshold, blunted the activity of melatonin. These results suggest that the time-dependent effects of melatonin on specific rodent behaviors may be mediated by central synapses employing gamma-aminobutyric acid (GABA) as an inhibitory transmitter.

Animals↗