Heidrun Fink - Academia.edu (original) (raw)
Papers by Heidrun Fink
Neuropharmacology, 2011
Deficiencies in serotonergic neurotransmission are involved in the pathophysiology of depression.... more Deficiencies in serotonergic neurotransmission are involved in the pathophysiology of depression. Due to its modulatory effect on serotonin (5-HT) release, the 5-HT 1A-receptor is thought to play a decisive role in the therapy of this mood disorder. However, it is not fully understood how antidepressant effects are mediated by pre-and postsynaptic receptor sites. In this study we examined the impact of postsynaptic 5-HT 1A-receptor over-expression in corticolimbic areas of male and female mice on the performance in the forced swim-test (FST). Furthermore, we investigated their response to the serotonin selective reuptake inhibitor (SSRI) citalopram in comparison to the selective noradrenaline reuptake inhibitor reboxetine, as well as the partial 5-HT 1A-receptor agonists, buspirone and S 15535. Additionally, these drugs were evaluated in the open field-test in order to observe effects on motor activity. The density of 5-HT 1A-receptors in discrete corticolimbic regions was determined in detail by quantitative autoradiography with [ 3 H]8eOHeDPAT to investigate genotype as well as sex dependent differences in the expression pattern. [ 3 H]8eOHeDPAT binding differed depending on sex with female mice of both genotypes displaying higher receptor binding in distinct brain areas. In the FST untreated male but not female over-expressing (OE) mice showed an antidepressant-like behaviour compared to wild-type (WT) mice. Citalopram yielded an antidepressant effect without influencing locomotor activity in OE mice but not in WT mice. Reboxetine had no antidepressant-like effect in OE mice, but sex-dependently in WT mice. The two partial agonists, buspirone and S 15535 produced no antidepressant-like activity in both genotypes and sexes, but aberrant motor effects. The antidepressant-like phenotype of male transgenic mice accounts for an involvement of postsynaptic 5-HT 1A-receptors in the FST behaviour. In addition, the selective over-expression of postsynaptic 5-HT 1A-receptors in mice contributes to the antidepressant response to citalopram in the FST. Although further pharmacological analysis is required, the data provide novel support for a role of postsynaptic 5-HT 1A-receptors in the effects of SSRIs. This article is part of a Special Issue entitled 'Serotonin: The New Wave'.
Pharmacology Biochemistry and Behavior, 2000
European Journal of Neuroscience, 2005
Central serotonin [5-hydroxytryptamine (5-HT)] is involved in the aetiology of numerous disease s... more 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.
European neuropsychopharmacology, 1999
The transgenic rat TGR(mREN2)27 was generated to study mechanisms involved in the hypertensive pr... more 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.
Neuropharmacology, 2011
Deficiencies in serotonergic neurotransmission are involved in the pathophysiology of depression.... more Deficiencies in serotonergic neurotransmission are involved in the pathophysiology of depression. Due to its modulatory effect on serotonin (5-HT) release, the 5-HT 1A-receptor is thought to play a decisive role in the therapy of this mood disorder. However, it is not fully understood how antidepressant effects are mediated by pre-and postsynaptic receptor sites. In this study we examined the impact of postsynaptic 5-HT 1A-receptor over-expression in corticolimbic areas of male and female mice on the performance in the forced swim-test (FST). Furthermore, we investigated their response to the serotonin selective reuptake inhibitor (SSRI) citalopram in comparison to the selective noradrenaline reuptake inhibitor reboxetine, as well as the partial 5-HT 1A-receptor agonists, buspirone and S 15535. Additionally, these drugs were evaluated in the open field-test in order to observe effects on motor activity. The density of 5-HT 1A-receptors in discrete corticolimbic regions was determined in detail by quantitative autoradiography with [ 3 H]8eOHeDPAT to investigate genotype as well as sex dependent differences in the expression pattern. [ 3 H]8eOHeDPAT binding differed depending on sex with female mice of both genotypes displaying higher receptor binding in distinct brain areas. In the FST untreated male but not female over-expressing (OE) mice showed an antidepressant-like behaviour compared to wild-type (WT) mice. Citalopram yielded an antidepressant effect without influencing locomotor activity in OE mice but not in WT mice. Reboxetine had no antidepressant-like effect in OE mice, but sex-dependently in WT mice. The two partial agonists, buspirone and S 15535 produced no antidepressant-like activity in both genotypes and sexes, but aberrant motor effects. The antidepressant-like phenotype of male transgenic mice accounts for an involvement of postsynaptic 5-HT 1A-receptors in the FST behaviour. In addition, the selective over-expression of postsynaptic 5-HT 1A-receptors in mice contributes to the antidepressant response to citalopram in the FST. Although further pharmacological analysis is required, the data provide novel support for a role of postsynaptic 5-HT 1A-receptors in the effects of SSRIs. This article is part of a Special Issue entitled 'Serotonin: The New Wave'.
Pharmacology Biochemistry and Behavior, 2000
European Journal of Neuroscience, 2005
Central serotonin [5-hydroxytryptamine (5-HT)] is involved in the aetiology of numerous disease s... more 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.
European neuropsychopharmacology, 1999
The transgenic rat TGR(mREN2)27 was generated to study mechanisms involved in the hypertensive pr... more 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.