Serotonin receptor binding and mRNA expression in the hippocampus of fearful amygdala-kindled rats

Department of Psychology, University of Saskatchewan, 9 Campus Drive, Saskatoon, Sask., Canada S7N 5A5.
Neuroscience Letters (Impact Factor: 2.03). 04/2006; 396(1):38-43. DOI: 10.1016/j.neulet.2005.11.005
Source: PubMed


Amygdala kindling in rats increases fear behavior. The neural correlates of this fear are not well understood. In this experiment, we investigated the relation between serotonin receptor binding and mRNA expression and fearful behavior in amygdala-kindled rats. Rats received either 100 kindling stimulations or sham stimulations, and their fear behavior was subsequently assessed in an unfamiliar open field. Then, the rats were sacrificed and 5-HT transporter binding, 5-HT1A and 5-HT2A receptor binding, and 5-HT1A mRNA expression in several brain regions was assessed. The kindled rats were significantly more fearful in the open field than the sham-stimulated rats. They also had significantly more 5-HT1A receptor binding and mRNA expression in the dentate gyrus than the sham-simulated rats, and these increases in 5-HT1A receptor binding and mRNA expression were significantly correlated to the increases in fear. There were no significant differences between the kindled and sham-stimulated rats in 5-HT transporter binding or 5-HT2A receptor binding. These results suggest that alterations in 5-HT1A receptors in the dentate gyrus may play a role in the expression of kindled fear.

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Available from: Lisa E Kalynchuk
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    • "This is an important question because there is evidence that the behavioral comorbidities associated with TLE vary depending on the location of the epileptic focus. This is seen quite clearly in the preclinical kindling model of TLE, where kindling of the basolateral amygdala (BLA) or dorsal hippocampus (dHip) impairs hippocampal-dependent fear conditioning[14,21,22]and spatial learning in the Morris water maze and radial arm maze[23,24]and enhances unconditioned fear behaviors in the open-field test and elevated plus maze252627. In contrast, kindling of nonlimbic brain sites, such as the caudate nucleus (CN), has minimal effects onEpilepsy "
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    ABSTRACT: Seizures dramatically increase the number of adult generated neurons in the hippocampus. However, it is not known whether this effect depends on seizures that originate in specific brain regions or whether it is nonspecific to seizure activity regardless of origin. We used kindling of different brain sites to address this question. Rats received 99 kindling stimulations of the basolateral amygdala, dorsal hippocampus, or caudate nucleus over a 6-week period. After kindling, we counted the number of adult generated hippocampal neurons that were birth-dated with the proliferative marker bromodeoxyuridine (BrdU) to evaluate cell proliferation and survival under conditions of repeated seizures. Next, we counted the number of doublecortin immunoreactive (DCX-ir) cells and evaluated their dendritic complexity to determine if limbic and nonlimbic seizures have differential effects on neuronal maturation. We also quantified hippocampal brain-derived neurotrophin factor (BDNF) protein levels using an ELISA kit and assessed memory performance using a hippocampal-dependent fear conditioning paradigm. We found that limbic, but not nonlimbic, seizures dramatically increased hippocampal cell proliferation and the number of hilar-CA3 ectopic granule cells. Further, limbic kindling promoted dendritic outgrowth of DCX-ir cells and the number of DCX-ir cells containing basal dendrites. Limbic kindling also enhanced BDNF protein levels throughout the entire hippocampus and impaired the retrieval of fear memories. Collectively, our results suggest a relationship between limbic seizures, neurogenesis, BDNF protein, and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · May 2015 · Epilepsy & Behavior
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    • "Serotonin receptors are distributed throughout the CNS and several receptors have been implicated in anxiety-like behavior, especially the 5HT1A receptor has received more attention [31,32]. NMDA receptors are known to play an important role in synaptic development and plasticity and are thought to be involved in anxiety-like behavior [33]. "
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    ABSTRACT: Background Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Methods Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. Results In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. Discussion High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period.
    Full-text · Article · Sep 2014 · Behavioral and Brain Functions
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    • "On the contrary, in our citalopram study, we found that both kindling and citalopram increased 5-HT 1A receptors, although these effects were not apparent in the fluoxetine experiment. While this finding is not consistent with human studies of reduced hippocampal 5-HT 1A receptors in epilepsy (Hasler et al., 2007; Theodore et al., 2007), it does somewhat agree with studies using amygdala kindling (Kalynchuk et al., 2006), which showed upregulation of hippocampal 5-HT 1A receptors in the dentate gyrus. "
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    ABSTRACT: Due to the high comorbidity of epilepsy and depression, antidepressant treatment is commonly indicated for patients with epilepsy. Studies in humans and animal models suggest that selective serotonin reuptake inhibitors (SSRIs) may reduce seizure frequency and severity, and these drugs are generally considered safe for use in epilepsy. No studies have investigated the effects of SSRIs on epileptogenesis, the neurobiological process underlying the development of the epileptic state. The effect of continuous infusion of the SSRI, fluoxetine (10mg/kg/day sc), versus vehicle control on amygdala kindling was examined in adult male Wistar rats. Seizure threshold and kindling rates were compared between SSRI-treated rats and controls. The study was then repeated examining the effect of a different SSRI, citalopram (10mg/kg/day sc), versus vehicle control. Hippocampal mRNA expression of the serotonin transporter (SERT) and the 5-HT1A receptor was examined in the brains of the rats post-mortem. Treatment with either fluoxetine or citalopram significantly accelerated kindling epileptogenesis, as evidenced by fewer stimulations to reach Class V seizures compared to their respective vehicle-treated group (p<0.01 for both drugs). Seizure duration was also increased in fluoxetine-treated rats. No differences in seizure threshold were observed between treatments (p>0.05). mRNA analysis did not reveal any molecular changes which were common to both treatments. The rate of epileptogenesis in rats is enhanced by chronic treatment with SSRIs. This could potentially have implications regarding the effect of SSRIs on the development or progression of human epilepsy.
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