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Biomedical subjects

P Södersten

Publications and source records attributed to P Södersten.

At least 19 recordsLinked to original sources
PubMed2001

Locus coeruleus noradrenergic lesions attenuate intraoral intake.

I.p. injections of DSP-4 in male rats decreased norepinephrine (NE) levels to varying degrees throughout the brain with 66.7% reductions in the hypothalamic paraventricular nucleus. Intake of intraorally infused sucrose was reduced for 14 days but daily pellet intake recovered within 5 days post-injection. Intraventricular NE restored intraoral sucrose intake in DSP-4-lesioned rats without affecting controls. Intraventricular infusion of neuropeptide Y (NPY) reduced intraoral intake in controls but had no effect in DSP-4-lesioned rats. NPY markedly inhibited intraoral intake in DSP-4-treated rats that also received NE. These data confirm studies showing that NPY decreases consummatory ingestive behavior and suggest that this inhibition involves ascending noradrenergic projections from locus coeruleus.

Adrenergic Agents↗
PubMed2000

Evidence that MK-801 stimulates intraoral intake by acting on hepatic afferents.

Satiety signals from the gastrointestinal tract travel via vagal afferents to the nucleus of the solitary tract (NTS) in the brain stem, the first central relay in a neural network which controls food intake. The non-competitive NMDA antagonist MK-801 facilitates food intake in rats by acting on the NTS. Here we report that hepatic portal vein infusion of MK-801 (25 or 50 microg/kg) increases intake of an intraorally infused 1 M solution of sucrose (by 113 +/- 9 and 132 +/- 11%, respectively) and that this effect is prevented by hepatic vagotomy. By contrast, jugular vein infusion of MK-801 fails to increase sucrose intake but induces forward locomotion, indicating activation of a central mechanism. These data suggest that MK-801 can stimulate food intake by acting peripherally on hepatic vagal afferents.

Animals↗
PubMed2000

NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior and sexual behavior.

Many studies have indicated that neuropeptide Y (NPY) stimulates and leptin inhibits food intake. In line with this, intracerebroventricular injection of NPY (10 microg) stimulated and leptin (10 microg) inhibited intake of a sucrose solution when female rats were required to obtain the solution from a bottle. However, NPY inhibited and leptin stimulated intake if the solution was infused intraorally. Thus NPY stimulates the responses used to obtain food but inhibits those used to consume food, and leptin has the opposite effects. To test the specificity of these responses the sexual behavior of male rats was examined. NPY-treated males showed minor deficits in sexual behavior but chose to ingest a sucrose solution rather than copulate with a female if offered the choice. By contrast, leptin-treated males ingested little sucrose and displayed an increase in ejaculatory frequency if given the same choice. It is suggested that NPY is not merely an orexigenic peptide, but one that directs attention toward food. Similarly, leptin may not be an anorexic peptide, but one that diverts attention away from food toward alternate stimuli.

Administration, Oral↗
PubMed1999

CCK-8 can inhibit ingestive behavior by acting on the liver.

The possibility that cholecystokinin octapeptide (CCK-8) can inhibit ingestive behavior by acting on the liver was investigated. Male rats were trained to ingest an intraorally infused 1 M solution of sucrose and then injected with 10 microg CCK-8/kg. Intraperitoneal or hepatic portal vein, but not jugular vein, injection suppressed intake of the sucrose solution. Intraperitoneal injection was more potent than hepatic portal vein injection. Inhibition by hepatic portal vein injection was blocked by i.p. injection of 80 microg/kg of the CCK-A receptor antagonist L-364,718 or by hepatic vagotomy. The results support the hypothesis that CCK-8 can inhibit ingestive behavior via a hormonal action on the liver.

Animals↗
PubMed1999

Evidence of splanchnic-brain signaling in inhibition of ingestive behavior by middle molecules.

Anorexia, nausea, and vomiting are common symptoms of uremic intoxication. Fractions in the middle molecule weight range, isolated from normal urine and uremic plasma ultrafiltrate, inhibit ingestive behavior in the rat. To investigate their site of action and specificity, male rats were injected intraperitoneally, intravenously, or intracerebroventricularly with concentrated fractions of uremic plasma ultrafiltrate or normal urine (molecular weight range: 1.0 to 5.0 kD) and tested for ingestive and sexual behavior. An intraperitoneal injection of 0.5 ml of urine fraction (10:1) or 2.0 ml of uremic plasma ultrafiltrate fraction (25:1) inhibited carbohydrate intake by 76.3 and 45.9%, respectively, but an intravenous injection had no effect. However, intravenous injection of higher doses inhibited carbohydrate ingestion. An intracerebroventricular injection of 5 or 10 microl of urine (20:1) middle molecule fraction inhibited carbohydrate intake by 13.4 and 41.6%, respectively. An injection of 5 or 10 microl of uremic plasma ultrafiltrate (125:1) middle molecule fraction inhibited carbohydrate intake by 22.6 and 49.5%, respectively. Injections of the corresponding fraction from normal plasma ultrafiltrate had no effect. Injection of urine or uremic plasma ultrafiltrate middle molecule fractions did not affect the display of sexual behavior. These results suggest that middle molecule fractions from uremic plasma ultrafiltrate or normal urine act in the splanchnic region and/or brain to inhibit food intake and that the effect is specific for ingestive behavior.

Animals↗
PubMed1998

CCK-8 inhibits ingestive behavior in rats with lateral hypothalamic 6-OHDA lesions.

Male rats were injected with 6-hydroxydopamine in the lateral hypothalamus and tested for ingestive behavior starting on the day after the injection. The rats did not eat food pellets but readily ingested an intraorally infused nutritive solution. If given three daily intraoral infusions, 6-hydroxydopamine-treated rats defended their body weight and were as sensitive to the inhibitory effect of cholecystokinin octapeptide on intake as controls. Dopamine was reduced by 94% in the dorsal striatum five days after the 6-hydroxydopamine injection. Noradrenaline and serotonin were less markedly affected. Thus, while appetitive ingestive behavior is disrupted, consummatory ingestive behavior and body weight regulatory competence are only marginally affected by massive damage to forebrain dopamine neural networks.

Animals↗
PubMed1997

Cholecystokinin, dopamine D2 and N-methyl-D-aspartate binding sites in the nucleus of the solitary tract of the rat: possible relationship to ingestive behavior.

Receptor autoradiography was used to investigate the distribution of brainstem binding sites for cholecystokinin, dopamine and N-methyl-D-aspartate with particular reference to the nucleus of the solitary tract of the rat, an area involved in the control of ingestive behavior. Binding sites for the A and B subtypes of the cholecystokinin receptor, labeled with [(125)I]cholecystokinin octapeptide sulfate in the presence or absence of antagonists for the devazepide (A) or L-365,260 (B) receptor, were present throughout the caudal rostral extent of the nucleus of the solitary tract, the A type predominating in the commissural, medial and gelatinous part and the B type in the lateral part. In the most rostral part of the medial nucleus of the solitary tract, both A and B receptors were present. Dopamine D2 receptors, labeled with [(125)I]NCQ-298, were found in all parts of the nucleus of the solitary tract. No binding to the dopamine D1 receptor, labeled with [(125)I]SCH-23982, was found in the brainstem. N-Methyl-D-aspartate receptors, labeled with [(3)H]dizocilpine maleate, were also present in the entire caudorostral extent of the nucleus of the solitary tract. Binding to cholecystokinin A receptors was co-distributed with [(125)I]NCQ-298 and [(3)H]dizocilpine maleate binding in the caudal and rostral parts of the nucleus of the solitary tract, and binding to cholecystokinin B receptors overlapped with [(125)I]NCQ-298 and [(3)H]dizocilpine maleate binding in the rostral nucleus of the solitary tract. These results are consistent with the hypothesis that cholecystokinin, dopamine and glutamate interact in the nucleus of the solitary tract in the control of ingestive behavior.

Animals↗
PubMed1997

Altered dopamine function in pathological gambling.

BACKGROUND: The possibility that monoaminergic neurotransmission is altered in pathological gambling was examined. METHODS: Monoamines and their metabolites were measured in CSF obtained at level L4-5 from ten pathological gamblers and seven controls. RESULTS: A decrease in dopamine and an increase in 3,4-dihydroxyphenylacetic acid and homovanilic acid was found. Noradrenaline and its metabolite 3-methoxy-4-hydroxyphenylglycol was also increased but 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were unchanged. CONCLUSION: It is suggested that the function of the dopaminergic system, possibly mediating positive and negative reward, and the noradrenergic system, possibly mediating selective attention, is changed in pathological gambling.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Cholecystokinin octapeptide inhibits carbohydrate but not protein intake.

Male rats ingested about half as much of an intraorally infused (1 ml/min) carbohydrate solution compared with a protein solution. Blood levels of cholecystokinin octapeptide (CCK-8) had increased to 13.6 +/- 1.4 and 16.7 +/- 1.7 pmol/l when the rats stopped ingesting carbohydrate or protein and continued to increase to 35.6 +/- 3.2 pmol/l 30 min after the carbohydrate meal and 34.4 +/- 3.5 pmol/l 60 min after the protein meal. Intraperitoneal injection of CCK-8 (0.6-5.0 micrograms) inhibited and injection of the CCKA-receptor antagonist L-364, 718 (20-80 micrograms) facilitated carbohydrate intake, but neither CCK-8 nor L-364,718 affected protein intake. The results suggest that CCK-8 is not involved in regulating the duration of a protein meal but may be involved in regulating carbohydrate intake. The postprandial period of suppression of protein intake correlated with the disappearance of some amino acids, e.g., Arg, Tyr, and Trp, in the blood, and this may be of importance for protein ingestion, since these amino acids are neurotransmitter precursors.

Amino Acids↗
PubMed1996

Influence of peritoneal dialysis solutions with glucose and amino acids on ingestive behavior in rats.

Continuous ambulatory peritoneal dialysis (CAPD) is often associated with malnutrition; reduced intake of nutrients due to anorexia is an important factor. The glucose load from glucose-based peritoneal dialysis (PD) solutions and amino acids from amino acid-based solutions may favor suppression of the appetite. To study this matter we used a new experimental model in free-moving, unstressed male Wistar rats (300 to 350 g) with feeding catheters channeled from the top of the skull to the oral cavity. When the rats recovered from surgery they were tested under standardized conditions by giving them an intraoral infusion (1 ml/min) of a solution containing 342 g/liter of the sucrose or 97 g/liter protein solutions while recording the time (volume) of ingestion. Control rats consumed 18.8 +/- 0.9 ml of the sucrose and 39.8 +/- 0.8 ml of the protein solutions. Injections of PD solutions with 13.6, 22.7, and 38.6 g/liter of glucose reduced the ingestion of sucrose by 12.4%, 23.6% and 36.1%, respectively, but did not affect the ingestion of protein. Injections of 30 ml of PD solutions containing 11, 18 and 31 g/liter of amino acids reduced the ingestion of both sucrose by 9.7%, 17.1% and 33.2% and of protein by 13.5%, 25.9% and 33.1%, respectively. We conclude that in our experimental model, the inhibition of appetite caused by peritoneal solutions containing glucose or amino acids seems to be specific for each nutritional constituent and not simply an effect of hyperosmolality or large filling volumes.

Adaptation, Physiological↗
PubMed1996

Middle-sized molecule fractions isolated from uremic ultrafiltrate and normal urine inhibit ingestive behavior in the rat.

Uremic patients with suppressed food intake may regain appetite soon after starting dialysis, presumably because of the removal of one or more toxic factors that suppress appetite. To investigate this matter, this study used a new experimental model in free-moving, unstressed male Wistar rats (300 to 350 g) with feeding catheters channeled from the top of the skull to the oral cavity. When the rats recovered from surgery, they were tested under standardized conditions by being given an intraoral infusion (1 mL/min) of a 1 M sucrose solution or a 97 g/L protein solution or a mixed solution of carbohydrate, protein, and fat (Fortimel (Nutricia Nordica AB, Stockholm, Sweden)) while the time (volume) of ingestion was recorded. Solutions to be tested for their ability to inhibit ingestion were injected intraperitoneally (lp) and the intraoral infusion was started 20 min later. Plasma ultrafiltrate was collected from end-stage renal failure patients by isolated ultrafiltration at the beginning of their first hemodialysis and pooled. Ultrafiltrate was also obtained by filtering pooled plasma from healthy volunteers in vitro, using the same type of dialyzer and cellulose acetate membranes as those used in the uremic patients. Morning urine samples from healthy volunteers were pooled and subjected to the same in vitro filtration procedure as the normal plasma. Intraperitoneal injection of 20 mL normal ultrafiltrate had no effect on sucrose ingestion, whereas injection of 20 mL uremic ultrafiltrate reduced the ingestion of sucrose solution by 23% and the ingestion of Fortimel by 17%. Ten mL of ultrafiltrate from normal urine reduced the sucrose intake by 42%. The pooled ultrafiltrates from normal and uremic plasma and normal urine were subjected to molecular filtrations using a series of membranes with known cut-off points. The filtrations yielded four concentrated fractions with molecular weight ranges of 0.1 to 0.5 kilodaltons (kd), 0.5 to 1 kd, 1 to 5 kd, and 5 to 10 kd, respectively; the plasma fractions were concentrated a factor of about 25:1 and the urine fractions by about 15:1. After an ip injection of 2 mL of each concentrated plasma fraction, only the 1 to 5 kd fraction from the uremic ultrafiltrate inhibited sucrose intake, whereas the corresponding fraction from the normal ultrafiltrate had no effect. After injection of 1, 3, and 5 mL of the concentrated fractions of uremic ultrafiltrate, a dose-dependent inhibition of sucrose intake was achieved with the 1 to 5 kd fraction and, to a lesser extent, with the 5 to 10 kd fraction. Intraperitoneal injection of 0.5, 1.0, and 2 mL of the concentrated 1 to 5 kd fraction, but not of the other fractions from normal urine, also resulted in a dose-dependent inhibition of sucrose intake. The 1 to 5 kd fractions from the uremic ultrafiltrate and the normal urine ultrafiltrate also inhibited protein intake in a dose-dependent manner. These results suggest that one or more toxic compounds in the middle-molecule weight range, which are normally excreted in the urine, accumulate in uremia and suppress food intake.

Animals↗