Biomedical subjects

J P Voigt

Publications and source records attributed to J P Voigt.

At least 19 recordsLinked to original sources

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↗

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

Sex specific behavioural alterations in Mas-deficient mice.

Male mice lacking the Mas protooncogene have been shown to exhibit an increased anxiety in the Elevated Plus Maze Task and sustained long-term potentiation in the hippocampus without effect on spatial learning in the Morris Water Maze Task. Here, we report behavioural studies in female mice lacking the Mas protooncogene. As for the males, we analysed the learning and anxiety behaviour using both behavioural tasks. With the exception of a trend to a better performance in the Morris Water Maze no differences were found in both tests between control and Mas-deficient females. This implicates that the lack of Mas protein influences spatial learning and anxiety in a sex-specific manner.

Animals↗

PubMed2000

Does increased endogenous CCK interact with serotonin to reduce food intake in rats?

The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1-9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake.

Animals↗

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

Learning and anxiety in angiotensin-deficient mice.

Angiotensin II in the brain was shown to be involved in mechanisms influencing cardiovascular and electrolyte homeostasis, anxiety and learning. Here, we report behavioural studies in mice lacking angiotensinogen. We analysed learning and anxiety related behaviour using the Morris water maze task and the elevated plus maze task, respectively. In both tests no differences were found between control mice and angiotensin-deficient mice. This implicates that angiotensin does not influence learning and anxiety-related behaviour in mice under normal conditions.

Angiotensin II↗

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

Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene.

The Mas protooncogene is a maternally imprinted gene encoding an orphan G protein-coupled receptor expressed mainly in forebrain and testis. Here, we provide evidence for a function of Mas in the central nervous system. Targeted disruption of the Mas protooncogene leads to an increased durability of long term potentiation in the dentate gyrus, without affecting hippocampal morphology, basal synaptic transmission, and presynaptic function. In addition, Mas-/- mice show alterations in the onset of depotentiation. The permissive influence of Mas ablation on hippocampal synaptic plasticity is paralleled by behavioral changes. While spatial learning in the Morris water maze is not significantly influenced, Mas-deficient animals display an increased anxiety as assessed in the elevated-plus maze. Thus, Mas is an important modulating factor in the electrophysiology of the hippocampus and is involved in behavioral pathways in the adult brain.

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

CCK-8S facilitates 5-HT release in the rat hypothalamus.

The effects of the neurotransmitter serotonin (5-HT) and the neuropeptide cholecystokinin (CCK) on food intake are well established. Based on pharmacological studies, an interactive model for 5-HT and CCK was proposed. The present microdialysis study was aimed to provide neurochemical evidence for a facilitatory effect of CCK-8S on 5-HT release in the lateral hypothalamus under in vivo conditions. The results indicate an increase of extracellular hypothalamic 5-HT both during food intake in previously food-deprived rats and also after systemic administration of 8 microg/kg and 40 microg/kg CCK-8s in food-deprived rats. The results show that peripherally administered CCK-8s induces central serotonergic effects, possibly related to feeding.

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↗

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↗

PubMed1996

Comparison of the satiating effect of the CCKA receptor agonist A71378 with CCK-8S.

The satiating effect of the selective cholecystokininA (CCKA) receptor agonist A71378 and the mixed A and B receptor agonist CCK-8S were compared in 24-h food-deprived rats. After systemic application of 1.6, 8.0, and 40 micrograms/kg A71378 or CCK-8S, respectively, food intake was measured for 24 h. During the first hour A71378 and CCK-8S decreased food intake similarly. Two and 4 h after treatment, the satiating effect of A71378 continued. In contrast, 2 h after administration of CCK-8S a slight effect was observed at the highest dose (40 micrograms/kg), which totally disappeared after 4 h. In summary, the effect of A71378 on food intake is longer lasting compared to CCK-8S.

Animals↗

PubMed1996

Memory-enhancing effects of benzodiazepines in mice.

In the present study, post-trial effects of clonazepam and diazepam on inhibitory avoidance learning under two different experimental conditions (i.e., 0.25 or 0.75 mA footshock) have been investigated. Both clonazepam (0.5 mg/kg) and diazepam (2 and 8 mg/kg) enhanced retention when administered immediately after the 0.25 mA footshock applied during training of the inhibitory avoidance task. In contrast, clonazepam and diazepam proved ineffective after the 0.75 mA footshock. The results suggest a post-training memory-enhancing effect of clonazepam and diazepam depending on the experimental conditions.

Animals↗

PubMed1996

Effects of cholecystokinin octapeptide (CCK-8) on food intake in adult and aged rats under different feeding conditions.

The effects of CCK on food intake were investigated under fixed feeding conditions in comparison to a test meal taken after 16 h of food deprivation. The experiments were performed on young adult rats (8 weeks old) as well on aged rats (23 months old). Intraperitoneal CCK-8 (8 and 40 micrograms/kg) significantly reduced the size of a test meal following 16-h food deprivation. This effect was independent of the age of the rats. However, under fixed feeding conditions neither of the doses used in this study reduced food intake in the young adult rats, whereas the highest dose of 40 micrograms/kg did so in the aged rats. These results suggest that the hypophagic effect of exogenous CCK-8 depends on experimental conditions, food intake being reduced after a period of food deprivation but not under a fixed feeding regimen in adult animals. Furthermore, the data suggest that age is a factor contributing to the complex behavioral actions of CCK, because only old animals were more susceptible to an anorectic action of CCK under the fixed feeding schedule. An explanation may lie in an interaction of other known behavioral effects of CCK (e.g., anxiogenic, mnemonic action) with its effects under the different feeding schedules.

Aging↗

PubMed1995

Evidence for the involvement of the 5-HT1A receptor in CCK induced satiety in rats.

The present study was designed to examine possible interactions between exogenous CCK and the 5-HT1A receptor subtype mediated serotonergic effects on feeding in rats. The somatodendritic 5-HT1A receptor agonist 8-OH-DPAT (0.32 mg/kg sc) evoked feeding in freely feeding rats. This effect was attenuated by treatment with CCK-8 (1, 5 and 25 micrograms/kg ip). In food deprived rats, CCK-8 (40 micrograms/kg ip) significantly reduced the size of a test meal. Treatment with the 5-HT1A receptor antagonist WAY-100135 (10 mg/kg ip) antagonized this anorectic effect of CCK-8. WAY-100135 on its own did not affect food intake. These results suggest the involvement of the 5-HT1A receptor subtype in mediating 5-HT-CCK interactions in the control of food intake in rats.

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