Biomedical subjects

E M Stricker

Publications and source records attributed to E M Stricker.

At least 91 records · Page 5Linked to original sources

PubMed1987

Central inhibitory control of sodium appetite in rats: correlation with pituitary oxytocin secretion.

In the present experiments we examined neurohypophyseal hormone secretion in various models of sodium appetite in rats. Basal plasma levels of oxytocin were found to be low in sodium-deficient adrenalectomized rats and in intact animals treated daily with desoxycorticosterone acetate, both of which groups drank large amounts of NaCl solution, whereas basal plasma levels of arginine vasopressin were neither stimulated nor suppressed. Conversely, sodium appetite consistently was inhibited by treatments that stimulated pituitary oxytocin secretion. However, sodium appetite was not inhibited by administration of exogenous oxytocin, nor was it stimulated by administration of an oxytocin receptor antagonist. These and other results suggest that sodium appetite may be inhibited by activity in the supraoptic and/or paraventricular nuclei, the location of the neurons responsible for the synthesis of oxytocin, and can be stimulated only when activity in those neurons is reduced. Whatever the final neural pathway, our data support the hypothesis that the control of sodium appetite is governed by inhibitory as well as excitatory central mechanisms.

Adrenal Glands↗

PubMed1987

Effect of dopamine-depleting brain lesions in rat pups: role of striatal serotonergic neurons in behavior.

Previous results from our laboratory have demonstrated that 3-day-old rats given dopamine (DA)-depleting brain lesions are spared the severe behavioral dysfunctions seen after comparable brain damage in adults. This behavioral sparing is accompanied by a sprouting of serotonin (5-HT)-containing neurons in the striatum. The present results extend these observations by demonstrating that rats given the brain lesions as 15- or 27-day-olds continue to suckle, wean, and grow into adulthood without exhibiting any obvious behavioral dysfunctions, yet striatal 5-HT levels do not increase. Moreover, combined destruction of DA- and 5-HT-containing neurons in 3-day-old rat pups also produced no obvious behavioral dysfunctions. These and other results indicate that increases in striatal 5-HT are not necessary for the behavioral sparing observed after DA-depleting brain lesions in neonatal rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Vasopressin release in response to nausea-producing agents and cholecystokinin in monkeys.

Administration of lithium chloride and copper sulfate to adult monkeys caused marked elevations in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. Emesis was produced in five of the seven animals given these agents, in support of nausea as the main stimulus to AVP release. A similar pattern of AVP release without OT release was found after administration of cholecystokinin (CCK). Although most monkeys vomited in response to 10 micrograms/kg of CCK, a significant increase in plasma AVP levels also was produced with a dose of 1 microgram/kg, which did not produce emesis in any animal. These findings are in marked contrast with previous results in rats, which indicated that lithium chloride, copper sulfate, and CCK each stimulated OT rather than AVP release. Despite this interspecies difference, the significant neurohypophysial hormone secretion in response to both nausea-producing agents and CCK suggests that AVP secretion in monkeys, similar to OT secretion in rats, might reflect activation of central pathways mediating nausea and/or inhibition of food intake, even when overt illness is not produced.

Animals↗

PubMed1987

Neurohypophyseal secretion in hypovolemic rats: inverse relation to sodium appetite.

Subcutaneous injection of polyethylene glycol (PEG) solution in rats produces exponential increases in secretion of arginine vasopressin (AVP) and oxytocin (OT) in proportion to the induced plasma volume deficits. Previously, we reported that acute water loads eliminated the neurohypophyseal hormone responses to hypovolemia, whereas hypertonic NaCl potentiated them. The present experiments indicated that AVP and OT secretion after PEG treatment were blunted by prior maintenance of rats on a sodium-deficient diet for 2 days. In contrast, plasma AVP and OT levels after PEG treatment were enhanced by prior adrenalectomy or ligation of the inferior vena cava or by concurrent administration of phentolamine in association with arterial hypotension. AVP and OT responses to hypovolemia were similarly potentiated in rats made uremic by bilateral nephrectomy or by puncturing their bladders. These results parallel previous findings that osmotic dilution and sodium deprivation each enhance the sodium appetite induced by PEG treatment in rats, whereas hyperosmolality, hypotension, and uremia each abolish it. Consequently, they support our previous hypothesis that sodium appetite is inversely related to the activity of hypothalamic oxytocinergic neurons.

Adrenalectomy↗

PubMed1987

Cholecystokinin and gastric distension activate oxytocinergic cells in rat hypothalamus.

Systemic administration of cholecystokinin octapeptide (CCK-8) prompts an abrupt increase in circulating levels of oxytocin (OXY) but not vasopressin (VP) in rats. The present study determined whether CCK-8 selectively stimulated OXY-secreting neurons in the hypothalamic supraoptic nucleus of pentobarbital-anesthetized male rats. Antidromically identified neurosecretory neurons were categorized into putative OXY- and VP-secreting cells on the basis of their firing patterns and response to peripheral baroreceptor activation. Of 36 OXY-secreting cells studied, 30 demonstrated a 50-200% increase in firing frequency within 2 min of administering CCK-8 by intravenous or intraperitoneal injection, whereas none of the eight VP-secreting neurons studied was activated. In related experiments, 4-10 ml of air were used to inflate an intragastric balloon in rats; 20 of 22 OXY-secreting neurons displayed an abrupt and readily reversible increase in firing frequency, whereas only 2 of 17 VP-secreting cells were activated. Gastric distension similarly elevated plasma OXY levels in unanesthetized rats with indwelling gastric cannulas. Together with previous findings that the effects of CCK-8 on OXY release were attenuated by gastric vagotomy, these observations clearly demonstrate the existence of a sensitive neural link between the stomach and the neurohypophysis in the rat.

Animals↗

PubMed1987

Recovery of chronotropic responsiveness after systemic 6-hydroxydopamine treatment: studies in the pithed rat.

In pithed rats, neurally mediated chronotropic responses to thoracolumbar stimulation were reduced substantially 1 day after animals were treated with the neurotoxin 6-hydroxydopamine (6-HDA), which produced a subtotal destruction of postganglionic sympathetic nerve terminals. However, the chronotropic responses of 6-HDA-treated rats recovered to near normal within 1 week despite 90% depletion of cardiac norepinephrine (NE). This recovery of function appeared to depend upon function in surviving sympathetic nerves, and was associated with increased synthesis and release of NE from those neurons as well as diminished inactivation of NE. The gradual development of post-junctional changes, most notably an increase in the density of myocardial beta adrenergic receptors, resulted in enhanced sensitivity to NE and contributed to cardiac function 3 weeks after 6-HDA treatment. In addition, the adrenal medulla increased its synthesis of catecholamines after 6-HDA treatment and thereby contributed to cardiac function, which was especially evident during prolonged sympathoadrenal stimulation. Some of these same adaptations have been observed when rats are subjected to chronic stress, and thus common mechanisms of neuroplasticity may mediate the sympathoadrenal responses to stress and to subtotal injury.

Adenylyl Cyclases↗

PubMed1987

Increased dopamine efflux from striatal slices during development and after nigrostriatal bundle damage.

Dopaminergic control over striatal targets appears to be retained in rats sustaining lesions of the nigrostriatal dopamine (DA) system as long as 5-10% of that projection remains. Similarly, during postnatal development, dopaminergic control over striatal neurons matures well before the innervation of striatum by the nigrostriatal bundle is attained. These observations suggest that enhanced efficacy of dopaminergic transmission may compensate for hypoinnervation of striatum after lesions or during development. To examine this hypothesis, striatal slices were superfused with Krebs bicarbonate buffer and effluent was collected and analyzed for endogenous DA. Electrical field stimulation (2 Hz) continuously delivered to slices prepared from intact adult rats increased DA efflux to 3-5 times the prestimulation rate within 10 min. Efflux then fell to approximately twice the basal rate over the next 20 min. DA efflux was also examined using slices prepared from adult animals given 6-hydroxydopamine 2-3 weeks earlier, and from 7-10-d-old rat pups. In each group, striatal DA levels were 10-40% of adult control values. Nevertheless, stimulated DA efflux from these slices attained the same rate as that observed with intact, adult slices. Thus, fractional DA efflux from these slices was several times higher than the control rate by the end of the stimulation period. This increased DA efflux appeared to be a consequence of both increased release and decreased reuptake of DA, as the fractional DA efflux from control striatal slices could not be increased to the rate seen in hypoinnervated slices using nomifensine (10 microM), an inhibitor of DA efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Long-term effects of dopamine-depleting brain lesions on spontaneous activity of type II striatal neurons: relation to behavioral recovery.

The long-term effects of dopamine (DA)-depleting brain lesions on behavior and spontaneous activity of Type II striatal neurons were measured in rats after intraventricular injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Spontaneous firing rates were increased relative to control values when recorded 4-8 days or 4-6 weeks postlesion in animals displaying aphagia, adipsia and akinesia. In contrast, spontaneous activity was not increased when recorded 4-6 weeks after the lesion in animals that had recovered from behavioral deficits. Other animals that had recovered from the effects of an earlier 6-OHDA treatment were given either a second injection of 6-OHDA or a systemic injection of haloperidol, a DA receptor antagonist. In both groups, discharge rates were elevated relative to control levels in association with a reinstatement of behavioral deficits. These results demonstrate that behavioral recovery after large DA-depleting brain lesions is associated with a return of spontaneous activity of striatal neurons to normal levels, and suggest that both behavioral and electrophysiological measures are dependent on the functioning of residual elements of the DA system.

Action Potentials↗

PubMed1986

Effects of intraventricular 6-hydroxydopamine on the dopaminergic innervation of striatum: histochemical and neurochemical analysis.

The impact of intracerebroventricular administration of 6-hydroxydopamine (6-HDA) on the dopamine (DA)-containing nigrostriatal projection was determined by regional histochemical and biochemical analyses. One week postinjection, we observed that tyrosine hydroxylase (TH)-positive terminals were almost completely absent from the medial portion of striatum but gradually increased in density toward the lateral margin of this structure. A similar gradient was indicated by fluorescence histochemistry and biochemical analyses of DA. In contrast, the 6-HDA-induced changes in TH activity and in dihydroxyphenylacetic acid content were less severe and showed little or no medial-to-lateral gradient. These high levels of TH activity and DOPAC content, relative to local DA concentrations, suggest an increase in the synthesis and release of DA from residual terminals that may serve to compensate for the brain damage. By 4 months postlesion, both histochemical and biochemical analyses indicated the presence of more DA terminals in striatum than there had been one week postlesion. This change was most markedly obvious in the medial striatum, which had been almost completely devoid of terminals at one week postlesion. Retrograde tracing experiments revealed that terminals appearing in the medial striatum at 4 months postlesion arise from the same region of the substantia nigra that innervates the medial striatum in the intact animal. Thus, no change in the topographic relation between substantia nigra and striatum occurred as a result of the lesion.

Animals↗

PubMed1986

Short-term effects of dopamine-depleting brain lesions on spontaneous activity of striatal neurons: relation to local dopamine concentration and behavior.

The spontaneous activity of striatal neurons was measured after dopamine (DA)-depleting brain lesions were produced in rats by the neurotoxin 6-hydroxydopamine. The extent of DA depletion was determined using tissue punches from the same regions of striatum in which cell activity was recorded. Results showed that the spontaneous activity of Type II neurons in either the medial or lateral striatum increased only when local DA depletions exceeded 90%; when local depletions were less than 90%, spontaneous firing rates of Type II neurons were equivalent to control values. This finding was consistent with additional observations that ingestive and motor behaviors of the same animals were not disrupted until striatal DA depletions exceeded 90%. It also was found that spontaneous firing rates of neurons in the lateral but not the medial striatum could be at control levels in animals clearly exhibiting aphagia, adipsia and akinesia.

Animals↗

PubMed1986

Oxytocin secretion in response to cholecystokinin and food: differentiation of nausea from satiety.

Administration of cholecystokinin (CCK) to rats caused a dose-dependent increase in plasma levels of the neurohypophyseal hormone oxytocin (OT). The OT secretion was comparable to that found in response to nausea-producing chemical agents that cause learned taste aversions. The effect of CCK on OT secretion was blunted after gastric vagotomy, as was the inhibition of food intake induced by CCK. Food ingestion also led to elevated plasma OT in rats, but CCK and aversive agents caused even greater OT stimulation. Thus, after administration of large doses of CCK, vagally mediated activation of central nausea pathways seems to be predominantly responsible for the subsequent decrease in food intake. Despite their dissimilar affective states, both nausea and satiety may activate a common hypothalamic oxytocinergic pathway that controls the inhibition of ingestion.

Animals↗

PubMed1986

Increased tryptophan hydroxylase activity in serotonergic nerve terminals spared by 5,7-dihydroxytryptamine.

Adult rats received intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) to destroy serotonin (5-HT)-containing nerve terminals throughout the brain. When the animals were killed 3 or 21 days later, we observed a marked decrease in 5-HT content in septum and hippocampus and a parallel decline in in vitro high affinity 5-HT uptake. 5-Hydroxyindoleacetic acid (5-HIAA) concentrations also were reduced but by a much smaller extent, resulting in significant increases in the ratio of 5-HIAA to 5-HT. These changes were accompanied by similar increases in the ratio of tryptophan hydroxylase (TPH) activity to 5-HT content. The relative increases in TPH activity resulted from two temporally distinct processes, the first of which appeared to be an activation that could be mimicked in vitro by Ca2+-dependent phosphorylation. We conclude that, after partial damage to 5-HT neurons, there is a compensatory increase in the synthesis and release of 5-HT from those terminals that remain.

5,7-Dihydroxytryptamine↗

PubMed1986

Molecular adaptations in catecholamine biosynthesis induced by cold stress and sympathectomy.

Chronic cold stress and chemical sympathectomy are known to increase the synthesis and release of catecholamines in the adrenal medulla. Chromaffin cells adapt to altered functional requirements by increasing the synthesis of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. In this study, we investigated the molecular genetic mechanisms underlying these changes in enzyme activity. Estimates of TH mRNA levels were obtained by RNA dot-blot analysis with a cloned TH cDNA hybridization probe. Exposure to cold produced a 4.3-fold increase in the relative abundance of adrenomedullary TH mRNA. Increases in TH mRNA levels (90%) also were observed in the brainstem of cold-stressed animals. The relative amount of TH synthesized in vitro in a rabbit reticulocyte cell-free system, programmed with adrenal poly(A)+RNA, increased 4.3 times in cold-stressed rats. Alteration in TH mRNA abundance appears to be specific, as we observed no significant difference in the levels of total RNA or poly(A)+RNA in this tissue. In addition, the relative abundance of adrenomedullary TH mRNA increased by 60% 4 days after systemic administration of the neurotoxin 6-hydroxydopamine. This increase was transient and disappeared 2 weeks after the lesion. Changes in TH mRNA levels after cold stress or sympathectomy were eliminated by denervation of the adrenal gland. These results indicate that alterations in the relative abundance of TH mRNA mediate changes in TH activity induced by chronic stress or sympathectomy, and that these changes require an intact sympathetic input.

Adrenal Medulla↗

PubMed1986

Rats given dopamine-depleting brain lesions as neonates do not respond to acute homeostatic imbalances as adults.

Rats given near-total dopamine-depleting brain lesions as neonates exhibit none of the severe sensorimotor or ingestive dysfunctions that result when adult rats are given comparable lesions. These experiments showed that the apparent sparing of function is incomplete; when tested as adults, the brain-damaged animals did not eat in response to acute glucoprivation, nor did they drink water and saline in response to hypovolemia. Indeed, after receiving these homeostatic challenges, the animals became much less able to simply move about. In contrast to these marked effects, the dopamine-depleted rats ate normally after glucoprivation when they were handled hourly instead of being left alone. Similarly, administration of caffeine permitted them to drink while hypovolemic. These and other observations suggest that some central neurons other than those containing dopamine are responsible for maintaining behavioral activation in rats after neonatal destruction of dopaminergic fiber systems in the brain and that the homeostatic challenges compromise their function and thereby disrupt behavior.

Adaptation, Physiological↗

PubMed1986

Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats.

Administration of lithium chloride, copper sulfate, and apomorphine to rats each stimulated the secretion of oxytocin (OT) and, to a much lesser degree, arginine vasopressin. These agents are assumed to cause visceral illness in rats because of their effectiveness in promoting the acquisition of learned taste aversions. CuSO4 had a greater effect on plasma OT levels when administered ip rather than iv, whereas LiCl did not, results suggesting that LiCl probably stimulates OT secretion by central chemoreceptor activation whereas CuSO4 acts predominantly by local peritoneal irritation. A causal role for circulating OT in the acquisition of learned taste aversions was not found. These and other findings suggest that peripheral levels of OT may represent a quantifiable marker of visceral illness in rats and therefore might be useful in the interpretation of behavioral studies in which learned taste aversions are produced, provided that other stimuli of neurohypophyseal secretion are absent.

Animals↗

PubMed1986

Enhanced sodium appetite in rats with lesions centered on nucleus medianus.

Recent experiments have demonstrated that rats with lesions of the ventral portion of nucleus medianus (vNM) frequently exhibit a chronic and robust hyperdipsia, which occurs only at night. This study indicates that the same brain damage may produce a nocturnal appetite for sodium that is similarly pronounced and persistent. Of 68 rats with vNM lesions, 33 were observed to drink at least 15 ml of 0.51 M NaCl solution per day, and 11 of them consumed more than 30 ml daily. The basis for this impressive consumption of saline is uncertain; the brain-damaged rats had normal sodium concentrations, renin activities, and aldosterone levels in plasma during basal maintenance conditions, and they conserved sodium in urine when maintained on a sodium-deficient diet. Nevertheless, the present results indicate that vNM and/or local fibers of passage may play an important role in the control of sodium appetite, as it does in the control of thirst.

Aldosterone↗

PubMed1986

Interaction of osmotic and volume stimuli in regulation of neurohypophyseal secretion in rats.

Adult male rats were injected subcutaneously with polyethylene glycol (PEG) solution, which causes hypovolemia by progressive isosmotic leaching of plasma fluid into a local edema. Plasma levels of arginine vasopressin (AVP) were found to increase exponentially in response to induced plasma volume deficits up to 40%. However, plasma AVP was reduced to basal levels when the rats were given either free access to drinking water or intragastric water loads that diluted plasma osmolality by only 3-6% despite continued hypovolemia. Administration of hypertonic NaCl stimulated AVP secretion as well. However, combined PEG and hypertonic NaCl treatments produced plasma AVP levels greater than expected from simple additivity of the independent effects of hypovolemia and osmotic concentration. Oxytocin secretion similarly was stimulated by treatment with either PEG solution or hypertonic NaCl, it was especially pronounced when both treatments were given, and it was inhibited by osmotic dilution despite marked hypovolemia. These effects are analogous to those seen when hypovolemia stimulates water intake but subsequent osmotic dilution inhibits thirst in PEG-treated rats.

Animals↗

PubMed1986

Gastric emptying of glucose loads in rats: effects of insulin-induced hypoglycemia.

Previous work has established that the increased food intake of rats in response to insulin-induced hypoglycemia can be inhibited by the intravenous infusion of fructose, a sugar that cannot cross the blood-brain barrier and nourish cerebral chemoreceptors, and that this effect of fructose is abolished by hepatic vagotomy. The present series of experiments examined the effects of these treatments on gastric emptying of various glucose solutions in rats. Gastric emptying of the administered loads decreased in proportion to increasing concentration of glucose solution but not by enough for caloric delivery to be regulated precisely. Insulin-induced hypoglycemia increased the rate at which the glucose solutions emptied from the stomach. This enhanced emptying was suppressed by infusion of fructose, and that suppression was eliminated by hepatic vagotomy. These and other findings support previous proposals that food intake is controlled in part by satiety signals reflecting the nutrient content of the stomach and in part by satiety signals related to the delivery of utilizable calories to the liver.

Animals↗