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A Rex

Publications and source records attributed to A Rex.

At least 19 recordsLinked to original sources
PubMed2006

Changes in extracellular hypothalamic glucose in relation to feeding.

The aim of the present in vivo microdialysis study was to investigate the relation between feeding and changes in glucose concentrations in the rat ventromedial hypothalamus (VMH). Absolute ambient glucose concentrations in VMH were 1.43 mm in non-deprived rats as compared to 0.94 mm after 24-h food deprivation. To examine whether feeding influences hypothalamic glucose, changes of glucose concentration over time were determined relative to a baseline. Experiments were conducted in relation to both, nutritional state (food-deprived rats vs. non-deprived rats) and feeding conditions throughout the experiment (freely feeding rats vs. rats without access to food). The results of this microdialysis study show clearly that glucose concentration in the VMH of rats increases significantly in relation to food intake. The data demonstrate that a 24-h food deprivation before the experiment further augments this increase (up to 350% from baseline) as compared to non-deprived conditions (up to 60% from baseline). However, the magnitude of food related increase in VMH glucose does not correlate with the individual amount of food eaten. In conclusion, the present study shows for the first time that VMH glucose concentrations increase with food intake in the early dark phase, indicating that such changes do not only occur after pharmacological treatment, but also under physiological feeding conditions. The results further indicate that the feeding related increase in VMH glucose depends on the nutritional state of the organism.

Animals↗
PubMed2005

Anxiety but not arousal increases 5-hydroxytryptamine release in the rat ventral hippocampus in vivo.

Central serotonin [5-hydroxytryptamine (5-HT)] is involved in the aetiology of numerous disease states, including depression and anxiety disorders. Studies have shown that exposure of rats to animal tests of anxiety increases extracellular 5-HT in the cortex or hippocampus determined by in vivo microdialysis. To discriminate whether this increase is caused by the aversive conditions of an animal test for anxiety or by an unconditioned stressor evoking mainly arousal, the present study investigates the effects of an unconditioned acoustic stimulus and exposure to the elevated plus maze (X-maze), respectively, on the release of 5-HT in the ventral hippocampus compared with hippocampal 5-HT release in the home cage and in a non-aversive unfamiliar environment in freely moving rats. Our results showed a distinct pattern of 5-HT release in the ventral hippocampus depending on the stimulus used. Exposure to the X-maze for 20 min was accompanied by an 'anxious' behaviour in the rats and increased extracellular 5-HT to 165% of basal release, whereas exposure to a less aversive 'deactivated' plus maze (115+/-6%) or to white noise for 20 min in the familiar surroundings of the home cage (98+/-6%) did not change hippocampal 5-HT release significantly, despite similar behavioural activation indicated by increased locomotor activity. While both the X-maze and white noise may model anxiety and stress to a certain extent, it seems that the X-maze is more aversive. The results suggest a close relationship between anxiety-related behaviour, but not arousal/non-specific behavioural activation, and 5-HT release in the ventral hippocampus.

Acoustic Stimulation↗
PubMed2004

Effect of 5-HT1A receptor activation on hypothalamic glucose.

The somatodendritic 5-HT1A agonist 8-OH-DPAT reduces serotonergic activity and stimulates feeding in freely feeding rats. Interactions between circulating glucose and 5-HT1A receptor expression related to feeding have been described. The aim of the present microdialysis study was to (1) describe the relation between feeding and glucose in the LH, (2) to investigate if peripherally administered 8-OH-DPAT itself has an effect on extracellular glucose in the lateral hypothalamus (LH) of conscious rats. Baseline glucose concentrations were significantly different in microdialysis samples obtained from food deprived rats compared to freely feeding rats. After re-feeding, a significant rise in glucose levels by 45% was observed in the formerly food deprived rats. In freely feeding rats, 8-OH-DPAT (0.3 mg/kg, i.p.) reduced glucose level in the LH significantly. The effect of 8-OH-DPAT on brain glucose was antagonized by pre-treatment with the 5-HT1A antagonist WAY 100635 (3 mg/kg i.p.) which had no effect on its own. The data indicate, therefore, that the effect of 8-OH-DPAT on hypothalamic glucose is mediated by 5-HT1A receptors. In contrast, the same dose of 8-OH-DPAT proven effective in the brain had no effect on peripheral glucose. Only a very high dose of the 5-HT1A agonist (1.8 mg/kg i.p.) had a hyperglycaemic effect in the periphery. In conclusion, the present results show for the first time, that glucose in the lateral hypothalamus increases with a meal. The data demonstrate furthermore 8-OH-DPAT-induced changes of hypothalamic glucose level, implicating 5-HT1A receptors being involved not only in the control of hypothalamic 5-HT as shown before, but also in the control of hypothalamic glucose.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Determination of NADH in frozen rat brain sections by laser-induced fluorescence.

Methods to assess metabolism are important analytical tools in neuroscience. The fluorophore nicotinamide adenine dinucleotide (NADH) is a parameter of cellular metabolism. NADH fluorescence was measured using a laser-based fluorescence detector with spectral and temporal filters. Distribution and intensity of NADH fluorescence were investigated in frozen brain sections. In sections containing hippocampus the intensity of NADH fluorescence was correlated to brain structures. In order to investigate the consequences of neurotoxic lesions, 5,7-dihydroxytryptamine was injected into the dorsal raphe nucleus 4 to 240 days prior to the measurement. NADH fluorescence decreased in the affected region by 50%, indicating that no recovery in metabolic activity had occurred.

5,7-Dihydroxytryptamine↗
PubMed2000

Feeding and 8-OH-DPAT-related release of serotonin in the rat lateral hypothalamus.

Based on the different effects of somatodendritic 5-HT1A agonist 8-OH-DPAT on food intake whether given to food-deprived rats or freely feeding rats, we hypothesized that the effects of 8-OH-DPAT on extracellular serotonin (5-HT) in the lateral hypothalamus (LH) will interfere with different feeding states, eventually resulting in different patterns of 5-HT release. In a microdialysis study we measured extracellular 5-HT in the LH after 8-OH-DPAT under four experimental conditions, i.e., in freely feeding rats with no food available, freely feeding rats with access to food, in food-deprived rats with no food available, and in food-deprived rats with good available after treatment. The results show a significant decrease of 5-HT release after 300 microg/kg 8-OH-DPAT (i.p.) in freely feeding rats. This effect is not seen when food is provided after drug treatment. In contrast, the same dose of 8-OH-DPAT has no effect on 5-HT release in food-deprived rats. In addition, providing food after drug treatment does not change the release pattern significantly in food-deprived rats, suggesting more complexity in the underlying mechanisms. The present study describes the effects of 8-OH-DPAT on 5-HT release in the LH, depending on feeding conditions and feeding-related behavioral states.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

From genotype to phenotype--behavior of the transgenic rat TGR(mRen2)27 as an example.

Transgenic techniques provide a tool to generate animals that differ from the wild-type by one or more genes, either by introducing foreign genes (transgenic animals) or by specific mutations of genes (knock-out animals). Most transgenic and knock-out animals are mice and not rats. The frequent use of rat models in the behavioral laboratory, however, will require the increasing application of transgenic techniques in this species. This paper reviews behavioral data from our laboratory as an example of characterizing the behavioral phenotype of a particular transgenic rat, the TGR(mRen2)27 rat. By describing the anxiogenic profile of this rat we also consider some problems associated with such an analysis, with the intention to raise issues that may also apply to studies of behavior in transgenic animals in general.

Animals↗
PubMed1999

Cortical NADH during pharmacological manipulations of the respiratory chain and spreading depression in vivo.

The nicotinamide adenine dinucleotide (NADH) is one of the main means for energy transfer in the mitochondrial respiratory chain and is an important parameter of cellular metabolism. NADH can be measured by its fluorescence and various fluorometric methods have been developed. In this study, a pulsed nitrogen laser combined with a fibreoptic set-up and photomultipliers was used to induce and measure NADH fluorescence on the cortical surface. The aim of the study was to assess the suitability of the laser induced spectroscopy for in vivo and on-line measurement of NADH in neuroscience and particularly for the assessment of neuronal metabolism. Changes in cerebral blood flow may affect fluorescence measurement. To assess the consequences of alterations in blood flow, the vasodilators glyceryl trinitrate and nimodipine and the vasoconstrictor endothelin-1 were applied. The induced hemodynamic changes were verified by colour Doppler sonography. The tests using the vasodilators showed that an increased blood flow in the brain increased not only NADH fluorescence but also the scattered light measured. The vasoconstrictor caused opposite effects. Insertion of a compensation method (subtraction of the scattered light) allowed the exclusion of hemodynamic artifacts. Effects of changes in the cellular metabolism were induced by sodium cyanide, an inhibitor of the mitochondrial respiratory chain, or by 2,4-dinitrophenol (2,4-DNP), an uncoupler of the oxidative phosphorylation. Sodium cyanide induced a transient increase of NADH fluorescence and 2,4-DNP decreased intracellular NADH fluorescence. Furthermore, the repercussions of cortical spreading depressions (CSD), a response of the brain to noxious stimuli, on cortical NADH fluorescence were determined. A single CSD decreased cortical NADH fluorescence for about 1 min, followed by a 5- to 10-min increase. The changes in NADH levels seem to correspond with the excitation and inhibition of neuronal metabolism, respectively. In summary, the measurement of NADH fluorescence using the laser technique allows the determination of changes in oxidative phosphorylation with high regional selectivity and time resolution.

2,4-Dinitrophenol↗
PubMed1999

Hippocampal 5-HT and NE release in the transgenic rat TGR(mREN2)27 related to behavior on the elevated plus maze.

The transgenic rat TGR(mREN2)27 was generated to study mechanisms involved in the hypertensive process. A characteristic of this rat is a high expression of the murine renin-2 gene in several peripheral tissues and in the brain. The high expression of the transgene is associated with increased local formation of angiotensin II. In a previous study, we studied for the first time the behavior of male TGR(mREN2)27 rat in the open field and on the elevated plus maze. There were no differences between TGR(mREN2)27 and SPRD-controls in locomotor activity measured in the open field. While placed on the elevated plus maze, however, the TGR(mREN2)27 rats showed a greater "anxiogenic" profile than the SPRD-rats. The present study was aimed to characterize neurotransmitter release involved in anxiety in hippocampus of TGR(mREN2)27 rats during exposure to the elevated plus maze. Exposure to the maze resulted in an increased intrahippocampal serotonin release with the same maximum both in the transgenic rats and in the control rats. However, the subsequent decrease was significantly faster in the TGR(mREN2)27 compared to the SPRD-controls. The latter suggests that the serotonergic system is functionally changed in the TGR(mREN2) rat, too. In contrast, norepinephrine release did not change during exposure to the maze and there were no significant differences in norepinephrine release between transgenics and controls.

Angiotensin II↗
PubMed1999

Behavioral and neurochemical differences between Fischer 344 and Harlan-Wistar rats raised identically.

Inbred Fisher 344 and outbred Harlan-Wistar rats were compared in the elevated plus maze, the black-and-white box, the social interaction test, and a modified open-field test, to assess the contribution of genetic factors to aversion-motivated behavior. All animals used were born and raised under identical conditions. Compared to the Wistar rats, the Fischer rats displayed a more pronounced fearful behavior in all tests. In a separate microdialysis study, the relationship between behavioral variations to biochemical differences was assessed, with serotonin (5-HT) release in the ventral hippocampus being measured during the elevated plus-maze test. Exposure to the elevated plus-maze induced an increase in hippocampal 5-HT in the (more anxious) Fischer rats but not in the (less anxious) Wistar rats. The results confirm the influence of genetic factors on emotionality in rats and demonstrate a close, although not simple, relationship between the serotonergic system and "anxiety-related" behavior.

Animals↗
PubMed1998

Major biological actions of CCK--a critical evaluation of research findings.

Cholecystokinin (CCK) is one of the first discovered gastrointestinal hormones and one of the most abundant neuropeptides in the brain. Two types of CCK receptors have been identified: (1) CCK-A receptors are mainly located in the periphery, but are also found in some areas of the CNS; and (2) CCK-B receptors are widely distributed in the brain. Major biological actions of CCK are the reduction of food intake and the induction of anxiety-related behavior. Inhibition of feeding is mainly mediated by the A-type receptors, whereas anxiety-like behavior is induced by stimulating B-type receptors. This paper presents new findings on the effects of the biologically active CCK agonists, CCK-8S, CCK-4, and A71378. The results reviewed suggest that the hypophagic effects of CCK are strongly dependent on the experimental design, sex, and age of the rats. For example, food intake measured during the night or after food deprivation is reduced by CCK-8S in young adult and aged rats, whereas, under fixed feeding conditions, CCK-8S does not inhibit food intake in young adult rats. The sensitivity to the hypophagic CCK effect increases with age in male and female rats; however, female rats are less sensitive to the CCK action. Further, using a nongenetic and non-stressful model of obesity due to unspecific postnatal overfeeding, the satiating effect of moderate CCK-8S doses is weaker in obese than in normal rats. Again, the hypophagic effect is more pronounced in male than in female obese and normal rats. Considering that aversive reactions in rats are markedly influenced by strain and breeding-line variations, research results in this area are critically reviewed. It is shown that anxiety-like symptoms can only be induced by a selectively acting CCK-B agonist, whereas mixed CCK-A and -B agonists and selective CCK-A agonists fail to change behavior in anxiety tests. CCK-4 induces stable and reproducible anxiogenic-like behavior only in certain rat strains. Moreover, CCK-4 effects can be demonstrated in the conflict test, in the ultrasonic vocalization test in rat pups, on the elevated plus maze, and in the black and white box, but not in the social interaction test. CCK has also been reported to modulate memory processes. On the one hand, CCK-8S and CCK-4 enhanced habituation to the novelty of a hole board. On the other hand, repeated administration of CCK-8S did not improve maze performance in aged rats. The literature on the behavioral pharmacology of CCK is rife with inconsistency and contradiction. The major biological actions of CCK depend on the receptor selectivity of the CCK fragments used and on organismic and procedural variables. All these variables potentially influence behavioral responses in rats. Therefore, in CCK research more attention should be paid to the importance of these methodological factors.

Animals↗
PubMed1998

Pharmacological evaluation of a modified open-field test sensitive to anxiolytic drugs.

In a recent study it has been shown that benzodiazepine receptor agonists attenuate novelty-induced suppression of feeding and increase the percentage of animals feeding in the open field. Food-deprived rats were placed in one corner of the open field containing food in the center. The number of rats beginning to eat in the first 5 min was recorded. In the present study this test was validated pharmacologically using known "anxiolytic" or "nonanxiolytic" drugs. The following substances (effective doses, given IP) increased the number of rats feeding within 5 min in the center of the open field: meprobamate (30.0-300 mg/kg), 8-OH-DPAT (10 and 30 microg/kg), ipsapirone (1.0 and 2.0 mg/kg), ritanserin (0.125-0.5 mg/kg), tropisetron (0.1-10.0 microg/kg), ondansetron (0.3-3.0 microg/kg), lisuride (0.28-0.55 mg/kg), morphine (0.3 and 1.0 mg/kg), propranolol (0.3 and 1.0 mg/kg), clozapine (1.0 mg/kg). Drugs without "anxiolytic" effects in other animal models or in humans, including amphetamine, apomorphine, haloperidol, sulpiride, and mCPP did not increase the incidence of food intake in this test. Ethanol and hexobarbital, in nonsedative doses, had no effect in this paradigm. Drugs and doses effective in the modified open-field test caused no increase in food intake in an independent food consumption test using food-deprived rats staying in the familiar cages. The results suggest that the modified open-field test can detect "anxiolytic" drug properties and is valid for the assessment of "anxiolytic" effects from different classes of drugs.

Animals↗
PubMed1998

Effects of cholecystokinin-receptor agonists on cortical 5-HT release in guinea pigs on the X-maze.

Exposure of guinea pigs to the elevated plus maze (X-maze), an animal model of anxiety, causes an increase of extracellular serotonin (5-HT) in the lateral prefrontal cortex monitored by microdialysis. The neuropeptide cholecystokinin (CCK) plays a role in the modulation of anxiety. To compare the roles of CCK receptors, the effects of the CCK-A receptor agonist A-71378, the CCK-A/B receptor agonist CCK-8S and the CCK-B receptor agonist BOC-CCK-4 on anxiety-related behavior and the 5-HT release in the prefrontal cortex were determined. None of the drugs changed the behavior of the guinea pigs and the cortical 5-HT release under resting conditions in the familiar home cage. A-71378 and CCK-8S had no effect on the behavior on exposure to the X-maze whereas BOC-CCK-4 induced an 'anxious' behavior. The results suggest that 'anxious' behavior induced by CCK is associated with selective CCK-B receptor stimulation. A-71378 inhibited the rise in 5-HT on exposure to the X-maze. CCK-8S had no effect and the anxiogenic BOC-CCK-4 potentiated the rise in 5-HT on the X-maze. Both CCK receptors mediate changes in 5-HT release under aversive conditions, but not in a resting state. The results suggest a receptor subtype-specific influence of CCK on behavior and 5-HT activity under aversive conditions.

Animals↗
PubMed1997

Cortical 5-HT-CCK interactions and anxiety-related behaviour of guinea-pigs: a microdialysis study.

Serotonin (5-HT) and cholecystokinin (CCK) are involved in the development of anxiety. There are only few data suggesting interactions between CCK and 5-HT under aversive conditions. In our study the cholecystokinin tetrapeptide (CCK-4) (10 microg/kg) induced 'anxious' behaviour and potentiated the increase of 5-HT release on the elevated plus maze (X-maze). The 'anxiolytic' 5-HT1A agonist 8-hydroxy-2-(di-n-propyl amino) tetralin (8-OH-DPAT; 0.3 mg/kg) reduced basal 5-HT and the increase in 5-HT release on the X-maze. 8-OH-DPAT given simultaneously with CCK-4, blocked the effects of CCK-4. The results demonstrate an interaction between CCK and 5-HT1A mechanisms via the influence on cortical 5-HT release.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

"Anxiolytic" action of diazepam and abecarnil in a modified open field test.

The effects of acutely administered diazepam and the beta-carboline abecarnil were examined in two animal models of anxiety in rats, and for their effects on food intake and locomotor activity. In the elevated x-maze diazepam (0.6-2.5 mg/kg) and abecarnil (0.03-0.3 mg/kg) induced anxiolytic-like effects. The second paradigm is based upon the suppression of feeding by exposure to a novel environment, adapted from Bodnoff et al. (1989). Food-deprived rats were placed in a corner of the open field containing food in the centre. The number of rats beginning to eat in the first 5 min was recorded. Diazepam (2.5-5.0 mg/kg) and abecarnil (0.01-0.3 mg/kg) increased the number of rats eating. Flumazenil, the benzodiazepine antagonist, was without effect, but antagonised the effects of diazepam and abecarnil. In a seperate series of experiments the effects of diazepam and abecarnil on feeding and locomotor activity were excluded as having influenced the the anxiolytic effects of these compounds in the animal models of anxiety.

Animals↗
PubMed1996

Strain differences in fear-motivated behavior of rats.

Studies have shown different and sometimes contradictory results in response to anxiolytic drugs. In the present study, the behavioral performance of rat strains, obtained from different breeders, was examined in four animal models of anxiety- or in exploration-related behavior to assess the potential contribution of genetic disposition or breeding factors to aversion-motivated behavior. Male rats: Wistar/Winkelmann, Wistar/Charles River, Wistar/BGVV, Lewis/Charles River, Fischer/Charles River, Brown Norway/Charles River were used in a conflict test in the open field, a free exploratory paradigm, social interaction test, and the holeboard test. The results show that robust behavioral differences in anxiety or exploration exist between different strains of rats and animals of one strain, obtained from different breeders. The differences shown in anxiety-related behavior might explain sometimes contradictory effects following the treatment with anxiolytic or anxiogenic drugs. The results indicate that genetic factors and breeding conditions substantially contribute to anxiety-motivated behaviors in animal models of anxiety. These differences in anxiety-related behavior may also be related to biochemical differences.

Animals↗
PubMed1994

Effects of cholecystokinin tetrapeptide and sulfated cholecystokinin octapeptide in rat models of anxiety.

The effects of the acutely administered cholecystokinin (CCK) agonists CCK tetrapeptide (BOC-CCK-4) and sulfated CCK octapeptide (CCK-8S) were examined in four animal models of anxiety in rats. In the elevated plus maze, BOC-CCK-4 reduced the time spent in the open arms and the number of entries into the open arms. BOC-CCK-4 but not the anorectic acting CCK-8S increased the suppression of feeding in a conflict paradigm based on novelty suppressed feeding in hungry rats. In the two-compartment black-and-white box, BOC-CCK-4 decreased the time spent and locomotor activity in the white compartment. In the ultrasound vocalization test, using rat pups separated from the mother, BOC-CCK-4 increased the number of distress calls. No evidence was found for inducing anxiety-like behaviour by CCK-8S.

Animals↗
PubMed1993

Effect of diazepam on cortical 5-HT release and behaviour in the guinea-pig on exposure to the elevated plus maze.

Previous studies have used the elevated plus maze to test for "anxiolytic" drugs in rats. The present study demonstrates that guinea-pigs handled daily from birth exhibit similar behaviour to rats on the plus maze. Pretreatment with diazepam (1.0 mg/kg) significantly increased the time the animals spent in the open arms and amount of entries into the open arms. Using intra-cortical microdialysis on exposure of the guinea-pig to the elevated plus maze resulted in increased extracellular 5-HT in the frontal cortex. Diazepam reduced, but not significantly, the increase in extracellular 5-HT and produced an "anxiolytic" profile of behaviour. Pretreatment with the benzodiazepine antagonist flumazenil (10.0 mg/kg) fully antagonised the behavioural effects of diazepam. Flumazenil also reduced the effect of diazepam on the increase in extracellular 5-HT observed on exposure of the guinea-pig to the elevated plus maze. Flumazenil alone decreased basal extracellular cortical 5-HT but had no effect on behaviour in the elevated plus maze. The results show that an increase in extracellular 5-HT occurs in the guinea-pig exposed to aversive conditions. While it remains to be determined whether the "anxiolytic" effects of diazepam in the guinea-pig are causally associated with decreased extracellular 5-HT, it is of interest that the selective benzodiazepine antagonist also prevented the increase in basal extracellular 5-HT produced by the exposure to the elevated plus maze but had no effect on behaviour. Results indicate that there is no simple relationship between inhibition of 5-HT release and the "anxiolytic" action of benzodiazepines.

Animals↗