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Biomedical subjects

R D Dias

Publications and source records attributed to R D Dias.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of undernutrition during suckling on ATP and ADP hydrolysis by synaptosomes from the cerebral cortex of adult rats.

1. Early undernutrition can cause permanent functional changes in the central nervous system. Alterations in enzymes involved in neurotransmitter metabolism have been reported to result from early undernutrition. 2. In a previous study, we demonstrated that undernutrition during suckling decreases ATP and ADP hydrolysis by synaptosomes from cerebral cortex by about 20% of the value found in 20-day-old well-nourished rats (J. B. T. Rocha, C. F. Mello, J. J. F. Sarkis and R. D. Dias, British Journal of Nutrition, 63:273-283, 1990). In the present study, we investigated whether this deficit persists in synaptosomes from cerebral cortex of nutritionally rehabilitated adult rats. 3. Rats were undernourished from birth to 25 days of life by feeding their dams a 7% casein (w/w) diet, while well-nourished offspring were fed by mothers maintained on a 28% casein diet. 4. In contrast to the results previously obtained in young rats, the synaptosomes obtained from the cerebral cortex of early undernourished adult rats hydrolyzed ATP and ADP more efficiently than did those obtained from well-nourished rats. Specific activity (nmol min-1 mg protein-1, mean +/- SD) was 114.9 +/- 9.5 for undernourished rats (N = 8) vs 94.1 +/- 9.5 for well-nourished rats (N = 8) for ATP, and 50.4 +/- 6.1 (N = 8) vs 38.8 +/- 4.5 (N = 8) for ADP. These results suggest that the deficits found in young rats disappear in rehabilitated adult rats.

Adenosine Diphosphate↗
PubMed1990

Undernutrition during the preweaning period changes calcium ATPase and ADPase activities of synaptosomal fractions of weanling rats.

The presence of activities that hydrolyse externally added ATP to adenosine in synaptosomal preparations from various sources is well demonstrated. The hydrolysis of ATP to AMP can be mediated either by the concerted action of enzymes or by an ATP-diphosphohydrolase (EC 3.6.1.5; apyrase). Undernutrition during the preweaning period can delay the development of several enzymes involved in the metabolism of neurotransmitters or neuronal function. In young rats, the presence of an apyrase in synaptosomal preparations from cerebral cortex was investigated. The results suggested that the hydrolysis of externally added ATP and ADP can be mediated by a single enzyme. The effects of preweaning undernutrition on the hydrolysis of ATP and ADP were also investigated. In weanling rats, previous undernutrition caused a decrease of about 20% in the hydrolysis of both substrates in synaptosomal fractions.

Adenosine Diphosphate↗
PubMed1990

Ontogeny of ATP and ADP hydrolysis by cerebral cortex synaptosomes from rats.

In the present study, we examined the ontogeny of ATP and ADP hydrolysis by cerebral cortex synaptosomes from rats of various ages (0-, 7-, 14-, 21- and 60 to 90-day-old rats) in order to learn whether hydrolytic activity increases during the period of intense brain growth, as has been reported for other enzymes involved in neurotransmitter metabolism. The results demonstrate that ATP and ADP hydrolyzing activities increase in parallel from birth until the second postnatal week (about 4-fold), followed by a slight and statistically insignificant increase until the animal reaches adulthood. The maximum increase in nucleotide hydrolysis coincided with maximum brain growth, which may indicate a role for the enzyme in neurotransmission. Furthermore, the parallel development of both activities (ATPase and ADPase) strongly suggest that a single enzyme, an ATP diphosphohydrolase, is involved in ATP and ADP hydrolysis by the synaptosomal fraction.

Adenosine Diphosphate↗
PubMed1990

Effects of chronic treatment with high doses of chlorpromazine on ATP and ADP hydrolysis by synaptosomal fractions from the rat caudate nucleus.

Several studies have indicated that chlorpromazine and its metabolites affect ATP hydrolysis by brain and liver plasma membranes in vitro. The present report examines whether chronic treatment (12 days) with high doses of chlorpromazine (10 and 40 mg/kg) could affect ATP and ADP hydrolysis by synaptosomal fractions from the rat caudate nucleus. Both doses of chlorpromazine caused significant and parallel decreases (23 to 31%) in the ATP and ADP hydrolysis. The parallelism between the effects of chlorpromazine on ATP and ADP hydrolysis suggests the participation of a single enzyme (ATP diphosphohydrolase) in nucleotide hydrolysis.

Adenosine Diphosphate↗
PubMed1989

Synaptosomal apyrase in the hypothalamus of adult rats.

1. The synaptosomal fraction isolated from hypothalamus of adult rats on a sucrose density gradient hydrolyzes the labile phosphates from ATP and ADP, thereby satisfying the general definition of apyrase activity. 2. The parallel behavior of ATPase and ADPase activities under different reaction conditions suggests the presence of a "true" apyrase enzyme. The optimum conditions for the reaction are the same for both nucleotides: pH 8.0, 0.6 mM nucleotide and 1.5 mM cation. At temperatures between 10 and 40 degrees C, both activities increase with no change in the ATP/ADP hydrolysis ratio. Thermal inactivation or inhibition of the enzyme activity by iodoacetamide, p-hydroxymercuribenzoate or 2-mercaptoethanol affected the hydrolysis of both substrates in a similar manner. 3. Adenylate kinase and pyrophosphatase activities were not detected in the preparation. 4. The enzyme is located on the outer surface of the synaptosomal membrane: intact and lysed synaptosomes have similar activity and the supernatant obtained by centrifugation of intact synaptosomal preparations does not hydrolyze ATP or ADP.

5'-Nucleotidase↗
PubMed1988

Memory facilitation by posttraining and pretest ACTH, epinephrine, and vasopressin administration: two separate effects.

Rats were trained in a step-down inhibitory avoidance task using a 0.3-mA, 2-s, 60 Hz footshock and tested 24 hr later. The animals received, 1 min after training and/or 5 min before testing, an ip injection of saline, ACTH (0.2 microgram/kg), lysine-vasopressin (10 micrograms/kg), epinephrine (5 micrograms/kg), naloxone (0.4 mg/kg), or a combination of naloxone with one of the hormones. Both the posttraining and the pretest injection of the hormones enhanced retention test performance; the enhancement was larger in animals that received the two treatments. Posttraining, but not pretest, naloxone administration also caused an enhancement. However, posttraining naloxone potentiated, and pretest naloxone antagonized, the effect of the concomitantly injected hormones. These data show that the posttraining and the pretest effect of the hormones are independent, are due to different mechanisms, and can be additive. In addition, it does not seem possible to explain posttraining memory facilitation by the hormones as owing to an addition to the reinforcement.

Adrenocorticotropic Hormone↗
PubMed1986

Differential effect of posttraining naloxone, beta-endorphin, leu-enkephalin and electroconvulsive shock administration upon memory of an open-field habituation and of a water-finding task.

Rats were trained and tested in an open field for habituation of rearing responses, for a water-finding task, or for both tasks simultaneously. Training-test interval was 24 hr. The water-finding task consisted of locating a metal tube in one of the walls of the box, which was attached to a water bottle on the outside; animals were water deprived between training and testing. Retention was estimated by measuring the latency to lick from the tube on the test session. Rats learned this task either with or without water deprivation, also prior to training. Habituation learning (reduction of the number of rearings between the training and test session) occurred either simultaneously with the water-finding task or in animals trained without the water tube, so that they could not learn the water-finding task. As happens with many other tasks, training in the open field was followed by a large decrease of hypothalamic beta-endorphin immunoreactivity, attributable to a release of this substance. Posttraining IP naloxone (1.6 mg/kg) administration facilitated, and posttraining beta-endorphin (2.0 micrograms/kg), leu-enkephalin (5.0 micrograms/kg), or electroconvulsive shock (15 mA, 60 Hz, 2 sec) depressed the retention of habituation; this occurred regardless of whether the animals were trained and/or tested with or without water deprivation, and whether the task was acquired alone or simultaneously with the water-finding task. By contrast, none of these treatments had any effect on retention of the water finding task, acquired either with or without prior water deprivation. Thus, habituation was, and water-finding was not, sensitive to posttraining treatments known to affect endogenous opioids: the opioids themselves, their antagonist, naloxone, and electroconvulsive shock which releases brain opioids and causes naloxone-reversible retrograde amnesia. Learning of the water-finding task was merely incidental to exploration of the open field; it took place even when the animals were trained without the water tube. This suggests that the posttraining treatments that affect endogenous opioid function affect memory only of the task(s) that actually cause the release of brain beta-endorphin (in this case, probably habituation), and not of others that may occur simultaneously but are merely incidental (water-finding). A feature apparently common to the former is that they must directly involve either the recognition of novelty, or the initiation of an interaction with a new environment, or perhaps the habituation of such interaction.

Animals↗
PubMed1986

Distribution of proline endopeptidase activity in sub-synaptosomal fractions of rat hypothalamus.

1. Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Because brain contains relatively large amounts of this enzyme and because of its specificity it has been suggested that it plays a role in the metabolism of neuropeptides, acting both on their processing and their degradation. 2. Since the final steps of neuropeptide processing occur in the synaptic vesicles and the degradation of most of these peptides is believed to occur in the synaptic cleft, we studied the distribution of proline endopeptidase activity in sub-fractions of rat hypothalamus. 3. Proline endopeptidase activity is present in synaptosomal fractions and is released by hypo-osmotic shock. Its specific activity is higher in the synaptoplasma than in synaptic membranes or vesicles (7.98 vs 0.18 and 0.24 nmol min-1 mg protein-1 carbobenzoxy-glycyl-prolyl-sulfamethoxazole hydrolysis). 4. Inhibitory avoidance training, a situation which releases hypothalamic vasopressin and beta-endorphin, both in vitro substrates, did not affect the specific or total activity of proline endopeptidase in synaptosomal plasma membranes.

Animals↗
PubMed1985

Influence on memory of posttraining or pre-test injections of ACTH, vasopressin, epinephrine, and beta-endorphin, and their interaction with naloxone.

The intraperitoneal (i.p.) injection of ACTH 1-24 (0.2 microgram/kg), lysine--vasopressin (10.0 micrograms/kg) or epinephrine HCl (5.0 micrograms/kg) shortly after training or prior to testing caused memory facilitation of a step-down inhibitory avoidance task in rats, acquired with low intensity training footshocks (0.3 mA, 60 Hz). Naloxone HCl (0.4 mg/kg) potentiated their posttraining effect, but antagonized their pre-test effect. Naloxone on its own caused retrograde memory facilitation but had no effect on the test session. Posttraining human beta-endorphin (1.0 microgram/kg) was amnestic, and its pre-test administration enhanced retention. Both effects were naloxone-reversible. Neither the pre-test facilitation caused by beta-endorphin nor those caused by any of the other drugs (which are possible releasers of endogenous beta-endorphin) were observed in animals in which the influence of endogenous opioids was prevented at the posttraining period by the administration of naloxone. These results are compatible with, and considerably strengthen, the previously advanced hypothesis that learning of this task, and possibly others, depends on a state induced by beta-endorphin after training, and that it would normally be dissociated because this peptide is normally not released during test sessions. In addition, the posttraining facilitation caused by ACTH, vasopressin, and epinephrine stands out as an effect separate from, and in fact normally hindered by, posttraining beta-endorphin release.

Adrenocorticotropic Hormone↗
PubMed1985

Interaction between consecutive learnings: inhibitory avoidance and habituation.

Rats were submitted to step-down inhibitory avoidance training and to habituation of a rearing response to a tone with a 2-h interval between the two tasks, and were tested for retention of both tasks on the next day. When animals were trained first in inhibitory avoidance and then in habituation, retention of the avoidance behavior was impaired. When the animals were trained first in the habituation task and then in the avoidance task, retention of the two tasks was normal. The same results were obtained regardless of the order in which the two tasks were presented on the day of testing. This asymmetrical influence of habituation training on inhibitory avoidance retention could be due either to cognitive or, more likely, to task-specific neurochemical interactions.

Animals↗
PubMed1985

Response of the rat brain beta-endorphin system to novelty: importance of the fornix connection.

In control rats, a step-down inhibitory avoidance training trial using a 0.8 mA footshock, or simple exposure to the training apparatus without footshock, was followed by a decrease of beta-endorphin-like immunoreactivity measured in the hypothalamus and ventral thalamus. The effect of inhibitory avoidance training was also measured in rats submitted to a brain sham operation, to bilateral transection of the dorsal fornix, to anterior or to posterior hypothalamic deafferentation, to adrenal medullectomy, to an adrenal sham operation, to 16 daily ip injections of 0.2 mg/kg dexamethasone, or to 16 daily ip injections of 1 ml/kg saline. The diencephalic beta-endorphin-like immunoreactivity response to training was abolished by fornix transection and was unaffected by all other treatments. This suggests that the response is not mediated by anterior or posterior neural afferents to the hypothalamus, or by a hypersecretion of epinephrine by the adrenal medullae, or of ACTH by the pituitary gland. The response, instead, appears to require the integrity of the pathway that sends projections from the septo-hippocampal system to the hypothalamus. Previous evidence had suggested that the diencephalic beta-endorphin-like immunoreactivity response to training is a result of novelty, and the septo-hippocampal system has been postulated to play a role in the registration of novelty.

Adrenal Medulla↗
PubMed1985

The course of the decrease of hypothalamic beta-endorphin induced by training, and the development of the effect of beta-endorphin on the retrieval of inhibitory avoidance in rats.

Step-down inhibitory avoidance training or the simple exposure of rats to the training apparatus is followed by a decrease of hypothalamic beta-endorphin immunoreactivity at 0.1, 1.0 or 2.0 h after training. Immunoreactivity returns to normal at 6.0 h. The ip administration of 1.0 microgram/kg of human beta-endorphin 6 min prior to training produces an inhibition of the retrieval of the step-down task at 6.0 h, but not at 0, 1.0 or 2.0 h after training. This effect is reversed by a second injection of the substance immediately before testing. The possible physiological significance of this parallel development of the effect of beta-endorphin on retrieval and the depletion of the substance caused by training is discussed. The data indicate that retrieval is insensitive to the peptide when its hypothalamic stores are depleted.

Animals↗
PubMed1984

Involvement of alpha-adrenergic receptors in the amnestic and anti-amnestic action of ACTH, beta-endorphin and epinephrine.

The post-training administration of ACTH1-24 (0.2 microgram/kg), human beta-endorphin (1.0 microgram/kg) or epinephrine HC1 (5.0 micrograms/kg), intraperitoneally, caused retrograde amnesia for a step-down inhibitory avoidance task in rats, and their pre-testing administration reversed this effect. The concomitant administration of the alpha 2-adrenergic receptor blocker, yohimbine HC1 (2.0 mg/kg), antagonized both the post-training amnestic and the pre-testing anti-amnestic effects of the three substances. The anti-amnestic effect of epinephrine, but not that of ACTH or beta-endorphin, was also antagonized by the alpha 1-adrenergic receptor blocker, prazosin HC1 (2.0 mg/kg). These findings suggest that alpha 2-adrenergic receptors are involved both in the amnestic and in the anti-amnestic effect of ACTH, beta-endorphin and epinephrine at the doses used, and that, in the case of the anti-amnestic effect of epinephrine, alpha 1 receptors also are involved. It seems likely that memory regulation by post-training and pre-testing ACTH and beta-endorphin requires the concomitant activity of alpha 2-adrenergic mechanisms, either central or peripheral.

Adrenocorticotropic Hormone↗
PubMed1984

Effect of various behavioral training and testing procedures on brain beta-endorphin-like immunoreactivity and the possible role of beta-endorphin in behavioral regulation.

Beta-Endorphin-like immunoreactivity is reduced in the rat diencephalon after the animals are exposed for the first time to any of the following behavioral situations: 50 tones (habituation), 50 tone-footshock shuttle avoidance trials, one step-down inhibitory avoidance trial, simple exposure to the avoidance apparatus with no footshocks, or inescapable shock. The effect is not observed when animals are exposed to any of these situations for a second time. The reduction of brain beta-endorphin-like immunoreactivity is attributable to release and subsequent metabolism of the substance, and correlates with the novelty inherent in the diverse training or test situations. The role of beta-endorphin in behavior is discussed in the light of these and previous results which showed that it causes both retrograde amnesia and a facilitation of retrieval. The substance would appear to serve an adaptive function when animals are exposed to a new experience, by inducing a temporary forgetting of the experience together with (or leading to) a state of alertness or preparedness for what may happen next.

Acoustic Stimulation↗
PubMed1983

The influence of adrenergic receptor antagonists on the amnestic and antiamnestic actions of adrenaline and tyramine.

The posttraining IP administration of adrenaline (epinephrine) HCl (5.0 micrograms/kg) or tyramine HCl (1.0 mg/kg) causes retrograde amnesia for a one-way step-down inhibitory avoidance task in rats. The effect is cancelled by the simultaneous injection of the alpha 2-adrenergic receptor antagonist yohimbine HCl (2.0 mg/kg) or of the beta 1 - beta 2 blocker propranolol HCl (2.0 mg/kg). The amnestic effect of posttraining adrenaline or tyramine is counteracted by the administration of adrenaline or tyramine prior to testing: each drug has a greater antiamnestic effect against itself than against the other drug. The antiamnestic effect of tyramine and adrenaline is antagonized by the simultaneous administration of prazosin or yohimbine, but not by that of propranolol. We conclude that the posttraining amnestic effect of adrenaline and tyramine is mediated by alpha 2 receptors (probably postsynaptic) and that it does not reflect a storage deficit, since memory can be restored by an appropriate treatment given before the test session. The antiamnestic effect of adrenaline and tyramine is mediated both by alpha 1 and by alpha 2 receptors, and probably reflects the dependency of mechanisms that make stored information available for retrieval on circulating catecholamines. The present findings provide no clue as to the anatomical distribution of the adrenergic receptors involved in the amnestic or antiamnestic actions of adrenaline and tyramine.

Adrenergic alpha-Antagonists↗
PubMed1983

Effect of ACTH, epinephrine, beta-endorphin, naloxone, and of the combination of naloxone or beta-endorphin with ACTH or epinephrine on memory consolidation.

The effect on retention of the post-training intraperitoneal administration of ACTH1-24 (0.2 or 2.0 micrograms/kg), epinephrine HCl (5.0 or 50.0 micrograms/kg), human beta-endorphin (0.1 or 1.0 microgram/kg), naloxone (0.4 mg/kg), and of the combination of naloxone or beta-endorphin with ACTH or epinephrine was studied in two different but closely related step-down inhibitory avoidance tasks in rats: task 1 (5 cm high 25 X 25 cm platform; 0.5 mA continuous footshock) and task 2 (7 X 25 cm platform, 0.3 mA discontinuous footshock). In task 1, saline control animals showed good retention in a test session carried out 24 hr later; beta-endorphin, ACTH and epinephrine caused amnesia; beta-endorphin potentiated the amnesic effect of ACTH and epinephrine; and naloxone caused memory facilitation and reversed the amnesic effect of ACTH and epinephrine. In task 2, control animals showed poor retention; beta-endorphin caused amnesia at the dose of 0.1 but not 1.0 microgram/kg; the other three drugs caused memory facilitation; naloxone potentiated the facilitatory effect of ACTH and epinephrine; and beta-endorphin reversed it and transformed it into a deep amnesia. These findings suggest that an opioid-mediated amnesic mechanism modulates the effect of ACTH and epinephrine on memory consolidation, either by dampening that effect when training parameters tend to make it facilitatory, or by enhancing it when training conditions tend to make it amnesic. On the basis of these and previous data it seems likely that the amnesic effect of ACTH and epinephrine could be mediated by endogenous beta-endorphin release.

Adrenocorticotropic Hormone↗
PubMed1983

Memory as a state dependent phenomenon: role of ACTH and epinephrine.

Rats received an ip injection of saline, epinephrine HCl (5.0 micrograms/kg), or ACTH1--24(0.2 microgram/kg) immediately after training in a step-down inhibitory avoidance task, and an ip injection of saline, or epinephrine (0.5, 1.0, 2.0, 3.0, 5.0, or 10.0 mu/kg), or ACTH (0.02, 0.04 0.08, 0.12, 0.2, or 0.4 microgram/kg) 6 min prior to a test session of the same task 24 hr after training. Retention was excellent in the groups treated with saline after training, and poor in those treated with ACTH or epinephrine after training and tested under saline. The amnestic effect of the drugs was counteracted by their administration prior to testing, and there was a dose-response curve for this effect: partial recovery from amnesia was obtained with 20 or 40% of the amnestic dose and full recovery was obtained with 60 to 100% of that dose when the same drug was given after training and prior to testing; if the drugs given after training and prior to testing were not the same, full recovery was obtained only with twice the amnestic dose of the latter. These findings are consistent with the hypothesis that learning depends on the relation between the endogenous levels of these two hormones in the post-training period and during testing. The animals seem capable of discriminating between the two drugs only partially.

Adrenocorticotropic Hormone↗