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L Hernandez

Publications and source records attributed to L Hernandez.

At least 145 records · Page 8Linked to original sources
PubMed1989

Patterns of extracellular 5-hydroxyindoleacetic acid (5-HIAA) in the paraventricular hypothalamus (PVN): relation to circadian rhythm and deprivation-induced eating behavior.

Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-HIAA every 2 hr for 3 days. During the first 2 days the rats were given free access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4-hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection.

Animals↗
PubMed1989

Haloperidol given chronically decreases basal dopamine in the prefrontal cortex more than the striatum or nucleus accumbens as simultaneously measured by microdialysis.

Simultaneous microdialysis was performed in the prefrontal cortex, striatum, and the caudal region of the nucleus accumbens using implanted guide shafts with removable microdialysis probes. Extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured in response to acute and chronic haloperidol, an antipsychotic drug. Six rats received haloperidol (0.5 mg/kg, IP) while changes in DA and its metabolites were monitored for six hours. Then the microdialysis probes were removed and daily injections of haloperidol were given for 28 more days. Next the probes were reinserted, and a final haloperidol challenge was given. A control group of six rats was treated the same way but with saline. The first injection of haloperidol increased extracellular DA, DOPAC and HVA proving increased turnover in all three regions. A month later, after chronic treatment, basal DA and its metabolites decreased in just the cortex. DOPAC and HVA also decreased in the cortex and striatum, suggesting a decrease in turnover at these two sites. None of these changes occurred in the accumbens. The last haloperidol challenge after chronic treatment no longer increased extracellular DA in any of the three sites, but increased production of metabolites was still detectable. This suggests a lack of DA responsiveness in all three sites. In summary, chronic haloperidol affected each of the regions differently; DA metabolites decreased in the STR and PFC; basal DA decreased in the PFC.

Animals↗
PubMed1989

Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity.

In rats with perifornical lateral hypothalamic (LH) electrodes that induced feeding, self-stimulation through the same electrodes increased immediately after ventromedial hypothalamic (VMH) lesions and did not return to normal until food intake normalized and the rats had become obese. In a second experiment a unilateral far-LH lesion decreased both feeding and contralateral perifornical LH self-stimulation. In Experiment 3, 6-hydroxydopamine (6-OHDA) injected into the midbrain to destroy the ventral noradrenergic bundle (VNAB) caused hyperphagia and increased LH self-stimulation. In summary, VMH or VNAB damage increased feeding and self-stimulation; contralateral far-LH damage decreased both. These results confirm the earlier suggestion that the VMH region is necessary for normal inhibition of feeding and feeding reward as reflected in self-stimulation rate. Although massive 6-OHDA-induced depletion of the dopamine system that passes through the LH can cause starvation and impair self-stimulation, the results suggest that selective catecholamine depletion of ventral midbrain neurons with sparing of the A9 and A10 dopaminergic cells can disinhibit feeding and self-stimulation. In all three experiments LH self-stimulation and food intake covaried, which suggests that they are functionally related.

Animals↗
PubMed1989

S-adenosylmethionine, S-adenosylhomocysteine and DNA methylation levels in the liver of rats fed methapyrilene and analogs.

The antihistamine methapyrilene (hydrochloride) and four close structural analogs, methaphenilene, methafurylene, thenyldiamine and clorothen, were given to rats at a concentration of 0.1% in drinking water for 34 weeks. Only methapyrilene produced notable histopathological changes in the liver, bile duct hyperplasia and focal cellular change. Methapyrilene produced an early and persistent elevation in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, which was 2.8 times the control levels at 34 weeks; none of the other antihistamines produced so high a ratio or altered the ratio as early. Methapyrilene, but not the other antihistamines, produced a significant increase in the methylation of liver DNA at 20 and 34 weeks, as measured by the level of 5-methyldeoxycytidine. The increase in deoxycytosine methylation is so far the only detected effect of the carcinogen methapyrilene on DNA which is absent in rats treated with its non-carcinogenic analogs.

Aminopyridines↗
PubMed1989

Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behavior. Theoretical and clinical implications.

This minireview deals with the possible roles of monoamines in feeding and feeding disorders. The introduction sketches the results of earlier studies with local drug injections and selective neurotoxins which provided pharmacological evidence that monoamines can influence food intake and body weight. A table summarizing this evidence is used to list monoamine changes that could underlie anorexia or hyperphagia. It is apparent that abnormalities in the monoamines, along with their cotransmitters, could cause many forms of feeding disorder. It is proposed as a working hypothesis that several varieties of hyperphagia leading to obesity have a common element. This common factor is a change in excitability of a lateral hypothalamic reinforcement system as manifested in self-stimulation at a stimulation-bound feeding site. Understanding this feeding reward-aversion system helps us understand hyperphagia and anorexia. The neurochemistry of reward and aversion involves the monoamines. This paper focuses on dopamine and serotonin. The data support the hypothesis that dopamine systems projecting to the nucleus accumbens and other forebrain areas from the mid-brain ventral tegmental area (VTA) are important for approach and positive reinforcement in ingestive behavior and self-stimulation. Serotonin is hypothesized to facilitate satiety and inhibition of feeding reward in the hypothalamus. The next section abstracts our recent experiments that measured pharmacological and physiological release of the monoamines in the hypothalamus and nucleus accumbens during ingestive behavior and self-stimulation. In vivo microdialysis in freely moving rats suggested the following: (1) Norepinephrine was released in the paraventricular nucleus during the active, feeding period of the circadian cycle. (2) The serotonin metabolite 5-HIAA also increased in the PVN at the same time if there was food to eat. (3) Amphetamine infused into the lateral hypothalamus (LH) by reverse dialysis increased synaptic dopamine, norepinephrine, and serotonin. (4) The anorectic drug d-fenfluramine increased synaptic serotonin in the LH and also increased the dopamine metabolite DOPAC, suggesting that serotonin and dopamine in the LH might contribute to fenfluramine-induced satiety. Local d-fenfluramine injection into the LH or local infusion by reverse dialysis again increased serotonin and decreased 5-HIAA and interfered with local dopamine metabolism as reflected in decreased DOPAC and HVA. (5) Tryptophan, a serotonin precursor, given systemically at an anorectic dose, increased extracellular serotonin in the LH, but this effect was only detectable in food-deprived rats. This was seemingly pH independent (between 5.8 and 8). The passage other cations through CFo is strictly suppressed (even at pH 8 and with 300 mM NaCl in the medium).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal ovarian function.

We have demonstrated the selective secretion of high mol wt PRL series (big big PRL) in women with hyperprolactinemia and normal ovarian function. This observation suggests that big big PRL is immunologically similar, but biologically less active, than monomeric or little PRL. In this study we determined the molecular size heterogeneity of immunoreactive PRL in the serum from two ovulatory hyperprolactinemic women (subjects A and B) who had large amounts of serum big big PRL during a menstrual cycle and/or gestation. Serum samples obtained throughout the menstrual cycle (days 6, 10, 14, 17, 23, and 28, taking as day 1 the first day of bleeding) and pregnancy (weeks 7, 9, 11, 15, 20, 25, 30, 34, and 38) were fractionated by gel filtration chromatography. PRL was identified in column eluates by specific RIA. Two additional pregnant women, one with a bromocriptine-treated PRL-secreting adenoma (subject C), and a normal woman (subject D) were studied. Big big PRL was the predominant species throughout the different phases of the menstrual cycle in subject B, comprising 70-80% of the total immunoreactive PRL. Most of the remainder was big PRL, and little PRL was present in only small amounts (6-12%) during the luteal phase. During their pregnancies, the serum PRL in subjects A and B initially was mostly big big PRL, but later in gestation the PRL composition shifted from the high mol wt variants to little PRL. The infant's cord (subject A) and peripheral (subject B) serum at birth contained appreciable quantities of big big and big PRL, respectively. These results indicate that structural changes in PRL occur during pregnancy and the menstrual cycle which are probably influenced by the hormonal environment. In addition, the occurrence of larger mol wt PRL species in the serum of the infant of a hyperprolactinemic mother suggests that the presence of high proportions of big big PRL in the serum is genetically determined.

Adult↗
PubMed1989

Variability of serum phenytoin concentrations in nursing home patients.

A marked variability in serum phenytoin concentrations was observed in an elderly nursing home resident. To determine the prevalence of this problem, 15 frail nursing home patients who were receiving phenytoin therapy were studied over a mean follow-up period of 10.6 +/- 0.89 months. The mean number of serum phenytoin level measurements during this period was 13.1 +/- 1.5. For a given individual, there was no variation in phenytoin dose or preparation administered. All the patients had a difference of more than 50% between the highest and the lowest serum phenytoin levels, and in five patients (33%), the difference exceeded 150%. The change in serum phenytoin level was temporally related to influenza vaccination in only three patients. The form of phenytoin was not a significant determinant of the variability in this patient population, nor did enteral feeding have any effect. It is recommended that nursing home patients receiving phenytoin therapy have periodic serum phenytoin measurements obtained, even in the absence of seizures or classic signs of phenytoin toxicity.

Aged↗
PubMed1988

Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis.

Dopamine was measured by microdialysis in the nucleus accumbens of freely moving rats while they experienced rewarding food, brain stimulation and drugs. Extracellular dopamine increased 37% when the animals pressed a lever for food reward. Electrical stimulation of a lateral hypothalamic feeding-reward (self-stimulation) site caused a similar increase in dopamine, with or without food. At the site in the nucleus accumbens where rats will administer amphetamine to themselves, injections of amphetamine or cocaine increased extracellular dopamine five-fold. Thus amphetamine and cocaine increase dopamine in a behavior reinforcement system which is normally activated by eating. Conversely, the release of dopamine by eating could be a factor in addiction to food.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Phencyclidine (PCP) injected in the nucleus accumbens increases extracellular dopamine and serotonin as measured by microdialysis.

Phencyclidine (PCP; 20 micrograms in 0.5 microliter) was tested by local brain injection for neurochemical effects in the nucleus accumbens and striatum of rats. Changes in dopamine turnover could not be detected in postmortem tissue assays. In contrast, extracellular levels of dopamine significantly increased as measured by microdialysis in freely moving animals. PCP also increased extracellular levels of serotonin and decreased 3,4-dihydroxyphenylacetic acid (DOPAC), but did not change homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5HIAA). Microdialysis suggests that PCP acts in some dopamine terminal regions to increase extracellular dopamine and serotonin.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Feeding and hypothalamic stimulation increase dopamine turnover in the accumbens.

The hypothesis that the dopaminergic system plays a role in feeding behavior was tested in three experiments. First, microdialysis was performed in the nucleus accumbens (NAC) at 20 min intervals during free feeding in rats at 80% of normal body weight. Extracellular concentration of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) increased significantly during eating indicating an increase in DA turnover. Second, microdialysis samples were collected from the NAC during bar pressing with a) a signal light on and food available, b) the light on but no food available, c) neither light nor food. Only when food was available did extracellular DA, DOPAC and HVA increase significantly. This increase in DA turnover occurred in the accumbens but not in the ventral striatum. Third, electrical stimulation of the perifornical lateral hypothalamus (LH) that was capable of inducing feeding increased extracellular DA, DOPAC and HVA in the NAC. This occurred whether the animal had food to eat or not. The effect of LH stimulation on DA turnover resembled the effects of free feeding and operant feeding in Experiments 1 and 2. Perifornical LH stimulation did not increase dopamine turnover in the ventral striatum. The results show that perifornical LH stimulation activates the mesolimbic dopamine system and that dopamine release in the accumbens is involved in feeding. The increase in dopamine turnover outlasted the consummatory act. This suggests that accumbens dopamine may be related to sensory input, feeding reflexes, food reward or memory processes and not just to the consummatory act itself.

Animals↗
PubMed1988

Hypothalamic infusion of amphetamine increases serotonin, dopamine and norepinephrine.

Microinjections of amphetamine into the lateral hypothalamus are known to cause anorexia and hypodipsia. These effects are thought to be mediated by an action of amphetamine on the catecholaminergic terminals to release dopamine and norepinephrine and block reuptake. Direct evidence of neurochemical release was lacking; therefore microdialysis was used to measure monoamines and their metabolites in the extracellular fluid of the lateral hypothalamus while amphetamine diffused out through the microdialysis probe. Amphetamine infusion significantly increased serotonin, dopamine and norepinephrine; it decreased dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and did not change homovanillic acid (HVA). These results suggest that amphetamine releases dopamine, norepinephrine and serotonin and blocks reuptake which thereby retards neurotransmitter breakdown. The net effect was a quadrupling of extracellular monoamines which could react with postsynaptic receptors. This supports the hypothesis that the behavioral effects of amphetamine injections into the lateral hypothalamus are mediated by dopamine, norepinephrine and suggests, in addition, serotonin.

Amphetamine↗
PubMed1988

Sulpiride injections in the lateral hypothalamus induce feeding and drinking in rats.

Amphetamine injections into the lateral hypothalamus inhibit feeding. This effect is blocked by local administration of neuroleptics, suggesting a role for dopamine in feeding inhibition. However, the type of dopamine receptor involved in satiety is not known. Therefore, we tested the effect of intrahypothalamic injections of sulpiride, a specific D2 receptor blocker, on amphetamine anorexia in food-deprived rats, and on spontaneous feeding and drinking in satiated rats. Sulpiride attenuated by 36% the anorexia produced by intrahypothalamic injections of amphetamine. In satiated rats, sulpiride (8 micrograms/0.5 microliter) elicited feeding (mean food intake after sulpiride: 5.4 g, and after vehicle 1.6 g, p less than 0.001), and drinking (mean water intake after sulpiride: 12.3 ml, and after vehicle: 0.9 ml, p less than 0.001). A dose response relationship was found between sulpiride dose and feeding or drinking. Sulpiride-induced drinking was observed in the absence of food, showing that it is not a postprandial phenomenon. These results suggest that hypothalamic D2 receptors might be involved in feeding and drinking regulation.

Animals↗
PubMed1988

Cost containment of formalin-preserved stool specimens for ova and parasites from outpatients.

Three individual formalinized stool specimens from each of 123 patients were pooled and examined for ova and parasites. Results obtained from the pooled specimens were compared with those obtained with the three individual specimens used to make the pooled specimens. Of 123 sets examined, 92 were negative and 31 were positive for ova and parasites. The pooled specimens were positive and all individual specimens were negative eight times, whereas the pooled specimens were negative and the individual specimens were positive twice. The data indicated that the pooled system is a useful and economical method of screening for ova and parasites.

Animals↗
PubMed1988

Dexfenfluramine and feeding reward.

This review describes background experiments and new findings showing that dexfenfluramine inhibits self-stimulation of a lateral hypothalamic (LH) feeding-reward system. Earlier work suggested that self-stimulation excites a pathway to the ventral tegmental area (VTA), where the mesolimbic dopamine system is involved in self-administration of food and drugs. LH stimulation also excites taste neurons in the nucleus tractus solitarius (NTS). This helps explain why stimulation can induce feeding responses and also reward self-stimulation responses. Stimulation-induced feeding and self-stimulation are modulated by physiological signals that control an animal's appetite and body weight. An animal will self-stimulate at a slower rate after it has just eaten, or if it is overweight, or if it is given an anorectic dose of insulin. At the same time, responses to turn off automatic stimulation tend to increase. Paradoxically, racemic fenfluramine decreased both self-stimulation and stimulation-escape, which suggested overall lethargy, but new results show this can be avoided by using just the d isomer. Dexfenfluramine inhibited LH self-stimulation but not stimulation-escape. It also released serotonin in the LH, as shown by microdialysis. These results suggest that dexfenfluramine can release serotonin that has as one of its effects the inhibition of circuitry for feeding-reward.

Animals↗
PubMed1987

Long term administration of some antipsychotic drugs increases body weight and feeding in rats. Are D2 dopamine receptors involved?

Long term administration of the antipsychotic drugs thioridazine, trifluoperazine, haloperidol, and sulpiride increased body weight in rats. This effect was found to be sex dependent, that is, while female rats were prone to gain weight, male rats did not. Chlorpromazine and fluphenazine decreased body weight in male rats but did not affect females. The mechanism of body weight gain was investigated with sulpiride. A linear relationship between dose of sulpiride and body weight gain was found. Also, sulpiride increased caloric intake, and both actions were counteracted by bromocriptine, a specific D2 receptor agonist. These results confirm that antipsychotic drugs affect feeding and body weight and suggest that hyperphagia and body weight gain might be mediated by blockade of dopamine receptors of the D2 type.

Animals↗
PubMed1987

Simultaneous microdialysis and amphetamine infusion in the nucleus accumbens and striatum of freely moving rats: increase in extracellular dopamine and serotonin.

To test the effects of systemic and local amphetamine on dopamine and serotonin release in freely moving rats, guide cannulas were implanted in the nucleus accumbens and ventral striatum for removable 200 mu microdialysis probes. Comparing 45 min samples before and after IP amphetamine (2 mg/kg), dopamine (DA) in dialysate from the accumbens increased from a baseline of 3 pg/20 microliters to 11 pg/20 microliters whereas dopamine metabolites, DOPAC and HVA decreased. This was probably due to block of DA reuptake and inhibition of monoamine oxidase, MAO. Accumbens serotonin increased from a baseline of 8 to 11 pg/20 microliters. Changes in the ventral striatum were similar. In the second experiment, microdialysis was performed before and after local injection of amphetamine (4 micrograms) to reveal effects of amphetamine in the terminal area only instead of the whole brain. DA in the accumbens increased from 11 to 147 pg per sample; serotonin, from 11 to 107. The effect was even larger in the ventral striatum. DA increased from 12 to 409 pg/20 microliters; serotonin, 3 to 139. To avoid handling the rat or disturbing brain tissue in experiment three, amphetamine was infused via the microdialysis probe during ongoing dialysis sampling. Perfusate containing amphetamine was switched into the flow line which allowed roughly 10% or 4 micrograms to diffuse out into the extracellular space. During this 20 min, extracellular DA in the accumbens increased from a baseline of 10 pg/20 microliters to 300 pg/20 microliters sample. Serotonin increased from barely detectable to 60 pg/20 microliters. DOPAC decreased significantly; HVA and 5HIAA drifted lower.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗