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L Hernandez

Publications and source records attributed to L Hernandez.

At least 127 records · Page 7Linked to original sources
PubMed1990

Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus.

In rats with microdialysis probes in the perifornical lateral hypothalamus (PFH) a single injection of the D2 receptor blocker 1-sulpiride (20 mg/kg IP) significantly increased extracellular dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), but not 5-hydroxyindoleacetic acid (5-HIAA). This suggests that sulpiride crosses the blood-brain barrier and blocks D2 dopamine receptors in the PFH leading to increased dopamine turnover reflected in increased extracellular DOPAC and HVA. We conclude that D2 blockade in the hypothalamus could play a role in the hyperphagia and body weight gain observed in female rats under chronic administration of the antipsychotic drug, sulpiride.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Neurochemical effects of chronic haloperidol and lithium assessed by brain microdialysis in rats.

1. Psychotropic drugs ameliorate psychotic symptoms only after repeated administration. 2. To assess the neurochemical effects of chronic haloperidol and lithium administration, microdialysis was performed simultaneously in the prefrontal cortex, the nucleus accumbens, and the striatum after haloperidol, and separately in the lateral hypothalamus and the hippocampus after lithium. 3. Chronic administration of haloperidol decreased dopamine turnover in the prefrontal cortex and the striatum. It did not affect the nucleus accumbens detectably. 4. No tolerance to haloperidol developed in any of the three regions. 5. Lithium enhanced the response of the serotonergic system to amphetamine in the lateral hypothalamus but not in the hippocampus. 6. The antipsychotic effect of haloperidol might be related to dopamine turnover decrease in the prefrontal cortex. 7. The antidepressant effect of lithium might be related to enhancement of serotonin responsiveness in the hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Serotonin release in lateral and medial hypothalamus during feeding and its anticipation.

In the present experiments we extend previous findings that established a relationship between feeding behavior and hypothalamic serotonin as measured by in vivo microdialysis. The new result is hypothalamic release of serotonin in anticipation of eating when the animal sees and smells food. We have now verified brain serotonin peaks in four different ways: 1) a serotonergic reuptake blocker (fluoxetine 1 or 10 microM) in the perfusion medium raised basal levels of serotonin, 2) every sample was oxidized at two potentials using a dual potentiostat to confirm the voltage characteristics of each peak, 3) serotonin peaks were reduced by the selective serotonin cell body agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), thus helping confirm that most of the serotonin observed in these experiments was neuronal in origin, and 4) lateral and medial hypothalamic microdialysis probes were used simultaneously to monitor the degree of diffusion from one to the other. The results show that extracellular serotonin increases at both sites during preingestive events as well as during eating, but not afterwards.

Animals↗
PubMed1990

Tryptophan increases extracellular serotonin in the lateral hypothalamus of food-deprived rats.

Although it is well established that increases in tryptophan availability can increase brain serotonin synthesis, the effect of tryptophan loads on serotonin release is not as clear. We have used in vivo microdialysis in order to monitor extracellular serotonin in the lateral hypothalamus to examine this issue. Tryptophan methyl ester (100 mg/kg IP) was administered to ad lib-fed and 48-h food-deprived rats. The results suggest that a peripheral tryptophan load can elevate extracellular serotonin in food-deprived subjects more effectively than in food-replete subjects.

Animals↗
PubMed1990

Dopamine in the lateral hypothalamus may be involved in the inhibition of locomotion related to food and water seeking.

Experiments were conducted in male rats to assess the motor effects of bilateral intraperifornical microinjections of sulpiride, dopamine (DA) and other drugs. Sulpiride increased locomotion of the animals in all the experiments reported here. DA (10 micrograms) administered 5 minutes before sulpiride (8 micrograms) reduced the motor stimulant effect of the neuroleptic from 1601.3 +/- 337.6 to 742.5 +/- 180.4 counts/30 min. SCH 23390 (15 micrograms), haloperidol (2.5 micrograms) and atropine (18 micrograms) did not modify the locomotion level of animals acclimated to the actimeters. After carbachol (5 micrograms) the animals attained a level of hyperactivity (1459.5 +/- 146.5 counts/30 min) similar to that induced by sulpiride (1595.7 +/- 365.7 counts/30 min) in the same experiment. In other experiments DA (10 micrograms) administered 30 min before sulpiride again blocked the effect of 8 micrograms of sulpiride, and reduced the initial hyperactivity of food- and water-deprived animals previously familiarized with the actimeters (922.4 +/- 49.38 counts/15 min under saline, vs. 544 +/- 29 counts/15 min under DA). The same DA dose did not modify the initial spontaneous activity of nonfamiliarized nonfood-deprived rats (508.9 +/- 96.1 after saline vs. 520.9 +/- 47.1 after DA). These results suggest the presence of cells in the lateral hypothalamus involved in the control of locomotion. These experiments also suggest that locomotion triggered by the LH may be exploratory behavior essential to the search for water and food. As a corollary, DA in the LH appears to be involved not only in the inhibition of feeding and drinking but also in the inhibition of exploratory and food- and water-directed locomotion.

Animals↗
PubMed1990

Feeding can enhance dopamine turnover in the prefrontal cortex.

Fluctuations of cortical dopamine during feeding were examined by in vivo microdialysis. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured by high performance liquid chromatography and electrochemical detection. Food-deprived rats were trained to eat by pressing a bar for food when a light and a feeder were turned on. The day of the experiment a microdialysis probe was inserted in the prefrontal cortex (PFC) of the rats and dialysates were collected every 20 minutes while the light and the feeder were off. When the neurochemical baseline was stable the light and the feeder were turned on for 20 minutes only. During this time the rats ate (mean 204 pellets = 9.2 g) and DA increased about 55%, remained high for another 20 minutes and then gradually returned toward baseline levels. DOPAC increased 30% in the first 20 minutes after the eating bout. HVA increased 40 minutes after the eating bout. Histology showed the probes were located in the anteromedial region of the PFC. We conclude that dopamine turnover in the mesocortical system increases during feeding under the conditions used. The results are discussed in terms of the role of the PFC in food intake modulation.

Animals↗
PubMed1989

Enhancement of hydroxylation and deglycosylation of 2'-deoxyguanosine by carcinogenic nickel compounds.

The effects of nickel subsulfide (Ni3S2) and nickel chloride [Ni(II)] on hydroxylation and deglycosylation of pure 2'-deoxyguanosine (dG) and on hydroxylation of guanine (Gu) residues in calf thymus DNA in the absence or presence of hydrogen peroxide (H2O2) and/or ascorbate (Ascb) were studied with the use of high-performance liquid chromatography. Incubation of 0.75 mM dG with 5 mg Ni3S2/ml (particle size less than 5 microns) at 37 degrees C in aerated 50 mM Tris/HCl buffer, pH 7.4, resulted in slow hydroxylation of dG to 8-hydroxy-2'-deoxyguanosine (8-OH-dG). This effect was greatly enhanced by 20 mM H2O2. Ni(II) alone at concentrations up to 10 mM was inactive but produced 8-OH-dG in the presence of 20 mM H2O2; the latter caused no dG hydroxylation by itself. Both Ni3S2 and Ni(II) increased the formation of 8-OH-dG from dG exposed to H2O2 + Ascb. At pH 7.4 and constant concentration of H2O2 and Ascb (20 and 8 mM, respectively), Ni(II) over the concentration range 1-10 mM raised the hydroxylation yield by up to five times that without Ni(II). Also, addition of 7.5 mM Ni(II) more than doubled the hydroxylation yield of Gu residues by the 20 mM H2O2 + 8 mM Ascb mixture (pH 7.4) in denatured DNA and doubled it in native DNA. Ni3S2 and Ni(II) alone had no effect on deglycosylation of dG and did not significantly influence the slow rate of Gu production from dG reacting with H2O2 or Ascb at pH 7.4. However, Ni(II), unlike Ni3S2, increased the extent of dG deglycosylation when added to the dG + H2O2 + Ascb system; 10 mM Ni(II) increased deglycosylation by a factor of 2.5 in 24 h. Thus, nickel carcinogens were shown for the first time to cause and/or enhance both hydroxylation and deglycosylation reactions of dG which may contribute to the observed genotoxic and carcinogenic effects of this metal.

Ascorbic Acid↗
PubMed1989

Goldthioglucose causes brain norepinephrine and serotonin depletion correlated with increased body weight.

Goldthioglucose (GTG) injected i.p. in mice is known to cause hyperphagia and obesity which is related to ventromedial hypothalamic damage and norepinephrine (NE) depletion in females. In the present experiment 6 doses of GTG were tested in males. After 160 days the monoamine content of whole brain was measured. Norepinephrine (NE) and serotonin (SER) were depleted without changes in dopamine content. Brain NE and SER were both negatively correlated with body weight. These experiments extend earlier studies by suggesting that GTG obesity in mice may be caused by NE depletion in males as well as females and by suggesting that the obesity is also a function of serotonin depletion.

Animals↗
PubMed1989

Fenfluramine administered systemically or locally increases extracellular serotonin in the lateral hypothalamus as measured by microdialysis.

Microdialysis was used to monitor serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and the metabolites of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the perifornical lateral hypothalamus (PFH) of freely moving rats. Systemically administered d-fenfluramine (d-FEN) increased extracellular serotonin, DOPAC and HVA, while decreasing serotonin's metabolite 5-HIAA. Local application of d-FEN directly to the hypothalamic terminal region caused large increases in extracellular serotonin and had a tendency to decrease all 3 metabolites. This effect was confirmed when d-FEN was infused locally by reverse dialysis. These results provide direct evidence that the anorectic drug d-FEN can increase extracellular serotonin in the hypothalamus in vivo and suggest a serotonergic action in the perifornical region. This finding is consistent with our report that a meal also increases serotonin in this region.

Animals↗
PubMed1989

Feeding increases extracellular serotonin in the lateral hypothalamus of the rat as measured by microdialysis.

Microdialysis probes inserted into chronically implanted guide shafts allowed the collection of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) from the lateral hypothalamus of rats during feeding behavior. After the collection of baseline samples, animals were offered a palatable diet that they could only see and smell for 60 min, then they were allowed access to the food for an hour. An additional three samples were collected after food was removed. Extracellular serotonin increased during the first half hour of access when the animals actually ate the food, and then returned to baseline level throughout the remainder of the test. 5-HIAA decreased gradually with no increase during feeding. These data suggest that eating a meal of palatable food causes a short-term increase in extracellular serotonin in the lateral hypothalamus. This increased serotonin may play a role in the control of lateral hypothalamic feeding and reward.

Animals↗
PubMed1989

Nicotine infused into the nucleus accumbens increases synaptic dopamine as measured by in vivo microdialysis.

It has been postulated that addiction to nicotine is mediated by dopamine release in the mesolimbic system. It is possible that nicotine might act directly on the dopamine terminals to release dopamine. This hypothesis was tested by infusing nicotine through a microdialysis probe into the nucleus accumbens of freely moving rats. Dopamine, dihydroxyphenylacetic acid, and homovanillic acid from the extracellular space were collected by microdialysis and measured by high pressure liquid chromatography. Nicotine increased extracellular dopamine in a dose-related manner. Systemic injection of the nicotine antagonist mecamylamine blocked the dopamine increase induced by local nicotine. These results suggest that nicotine releases dopamine by a local action in the nucleus accumbens terminal area of the mesolimbic system. Presynaptic induction of dopamine release might play a role in nicotine addiction.

Animals↗
PubMed1989

Lack of portal-venous hypertension after an arterioportal fistula in the rat.

The hepatic effects of an end-to-side arteriovenous fistula between the right renal artery and the portal vein were studied in rats. Fifty rats underwent surgery and were studied 3, 12, 24 weeks and 1 year later; Another 15 rats were used as controls. Rats did not have any portohepatic abnormality. Portal and caval pressure were measured, and the liver was evaluated histologically. No statistically significant differences were achieved between the control portal (10.37 +/- 0.29 cm H2O) and vena cava pressures (1.22 +/- 0.19 cm H2O) and those of the experimental groups. The overall liver architecture remained unchanged. A progressive enlargement of the intrahepatic portal and hepatic veins was noted. No hypertrophy of the fibrous tissue into the portal triads, hypertrophy of the muscularis of the portal vein radicals, or wall sclerotic thickening was seen. The forward overflow compensatory mechanisms are discussed.

Animals↗
PubMed1989

Glutathione and lipid peroxide levels in rat liver following administration of methapyrilene and analogs.

The possibility was examined that the induction of tumors in rat liver by feeding methapyrilene, which is not mutagenic, is related to effects on glutathione levels and lipid peroxidation. Fischer 344 rats were given single-dose and multiple-dose treatments with the anti-histamine methapyrilene (MP), which is carcinogenic in rats, and with two non-carcinogenic analogs, methafurylene (MF) and thenyldiamine (TD) and the effects on malonaldehyde (MDA) formation and glutathione (GSH) levels in the liver were investigated. After a single dose, MDA levels were increased at 6 h by MF and TD and at 24 h by MP. MDA levels returned to normal after 30 h with MP and MF, but not with TD. Levels of MDA (and other TBA-reactive products) after four daily treatments were most elevated by TD, less elevated by MP, and were lowered by MF. Forty-two hours following treatment with both MP and MF, MDA levels had returned to normal, but in TD-treated animals MDA remained high. GSH levels were highest after MF and MP, and remained high at 42 h, but TD induced only a small increase. There appears to be increased lipid peroxidation in the liver as a result of treatment of rats with MP, MF and TD. The greater response induced by TD, as well as the increased liver GSH levels after repeated administration of all three drugs indicate that lipid peroxidation in rat liver is not a particular effect related to the liver carcinogen methapyrilene.

Aminopyridines↗
PubMed1989

Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

Adult↗
PubMed1989

Patterns of extracellular norepinephrine in the paraventricular hypothalamus: relationship to circadian rhythm and deprivation-induced eating behavior.

In order to clarify the physiological role of norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN), changes in extracellular levels of endogenous NE were measured in 11 freely-moving rats using microdialysis and high pressure liquid chromatography with electrochemical detection. To determine whether there was a circadian pattern of extracellular NE in freely-eating subjects, samples of dialysate from the vicinity of the PVN were collected and assayed for NE every 2 hrs for 48 hrs. The pattern of NE averaged across subjects was similar during both 24-hr periods, with a reliable peak at the beginning of the dark cycle and relatively stable levels at all other times. When these animals were subsequently deprived of food for 24 hrs, a gradual rise in extracellular NE was observed, ultimately increasing to 215% of the predeprivation level. When the animals were refed and NE measurements were continued at more frequent intervals, extracellular levels were found to decline during the first 20 min of eating, as well as over the next 3 hrs as food intake diminished. These patterns of extracellular NE, together with previous evidence, suggest that endogenous NE in the PVN plays a role in the initiation and/or maintenance of normal eating behavior at the beginning of the nocturnal feeding period, as well as after food deprivation.

Animals↗
PubMed1989

The appetite suppressant, d-fenfluramine, decreases self-stimulation at a feeding site in the lateral hypothalamus.

In prior studies rats showed a relative shift from self-stimulation to escape (i.e., from reward to aversion) following a large meal, obesity or anorectic doses of insulin. Racemic fenfluramine, on the other hand, decreased both self-stimulation and escape suggesting it had a general behavior suppressant property. To avoid the depressive, antidopaminergic effects of the l-isomer, this study tested the d-isomer which is primarily serotonergic. Rats were screened for stimulation-induced feeding and then trained to self-stimulate with one lever in 5-min periods that alternated with 5-min periods of automatic stimulation from which the animal could escape with a different lever. d-Fenfluramine (1.5-4.5 mg/kg IP) caused a dose-related decrease in self-stimulation. Stimulation-escape was relatively unaffected. This is interpreted as a decrease in feeding reward due to d-fenfluramine.

Animals↗
PubMed1989

Mechanism of the body weight increase induced by systemic sulpiride.

Long-term intraperitoneal administration of sulpiride induced body weight increase in female but not in male rats. The hypothesis that systemic sulpiride causes an endocrine unbalance which in turn causes body weight gain and hyperphagia was tested in four experiments. First, it was shown that even when they are on a high-fat diet male rats do not show body weight gain induced by systemic sulpiride. Second, sulpiride suppressed the estrous cycle. Third, gonadectomy prevented the body weight gain induced by systemic sulpiride in female rats. Fourth, estradiol simultaneously administered with sulpiride prevented the expected sulpiride-induced body weight gain. These results are discussed in terms of an hypothetical functional castration produced by systemic sulpiride. The well known hyperprolactinemia, induced by the pituitary D2 dopamine receptor blockade, might bring about an impairment of the steroidogenesis with subsequent decrease in estrogens level, which in turn might be responsible for the hyperphagia and body weight increase induced by systemic injections of sulpiride.

Animals↗