Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of treatment with anxiogenic or anxiolytic agents and exposure to acute restraint stress on emotional behavior in mice were examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e., total locomotor activity, numbers and duration of rearing and head-dipping, and latency to the first head-dipping. The typical benzodiazepine anxiolytics diazepam (0.05-0.5 mg/kg, i.p.) and chlordiazepoxide (0.5-4 mg/kg, i.p.) dose-dependently increased the number and duration of head-dips at doses that did not produce sedation. In contrast with these anxiolytics, the typical anxiogenic drugs N-methyl-beta-carboline-3-carboxamide (FG7142, 0.125-10 mg/kg, i.p.) and methyl-beta-carboline-3-carboxylate (beta-CCM, 0.1-2 mg/kg, i.p.) decreased both the number and duration of head-dips, and increased the latency to head-dipping. Moreover, decreases in the number and duration of head-dips, and an increase in the latency to head-dipping, were also observed in animals that were exposed to acute restraint stress. These effects of acute restraint stress were suppressed by treatment with diazepam at a dose that alone did not produce significant behavioral effects (0.1 mg/kg, i.p.). In addition, non-benzodiazepine anxiolytic flesinoxan (0.1 mg/kg, i.p.), a 5-HT1A receptor agonist, also had an effect on the restraint stress-induced decrease in head-dipping behavior. The present study shows that the changes in several exploratory behaviors could be objectively measured using our automatic hole-board apparatus. Therefore, this system can serve as a useful tool for evaluating the changes in various emotional states of animals. Moreover, we also found that treatment with anxiolytics or anxiogenics and exposure to acute restraint stress affected head-dipping behavior. These results suggest that changes in head-dipping behavior in the hole-board test may reflect the anxiogenic and/or anxiolytic state of animals.
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PMID:Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. 968 10

Altered regulation of 5-HT1A receptors is implicated in mood disorders such as anxiety and major depression. To provide insight into its transcriptional regulation, we previously identified a novel DNA element [14 bp 5'-repressor element (FRE)] of the 5-HT1A receptor gene that mediates repression in neuronal and non-neuronal cells (Ou et al., 2000). We have now cloned a novel DNA binding protein [five' repressor element under dual repression binding protein-1 (Freud-1)] that binds to FRE to mediate repression of the 5-HT1A receptor or heterologous promoters. Freud-1 is evolutionarily conserved and contains two DM-14 basic repeats, a predicted helix-loop-helix DNA binding domain, and a protein kinase C conserved region 2 (C2)/calcium-dependent lipid binding (CalB) calcium/phospholipid binding domain. An intact CalB domain was required for Freud-1-mediated repression. In serotonergic raphe cells, overexpression of Freud-1 repressed the 5-HT1A promoter and decreased 5-HT1A receptor protein levels, whereas transfection of antisense to Freud-1 derepressed the 5-HT1A gene and increased 5-HT1A receptor protein expression. Calcium-dependent signaling blocked Freud-1-FRE binding and derepressed the 5-HT1A promoter. Treatment with inhibitors of calmodulin or CAM-dependent protein kinase reversed calcium-mediated inhibition of Freud-1. Freud-1 RNA and protein were present in raphe nuclei, hippocampus, cortex, and hypothalamus, and Freud-1 protein was colocalized with 5-HT1A receptors, suggesting its importance in regulating 5-HT1A receptors in vivo. Thus, Freud-1 represents a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons and may play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression.
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PMID:Freud-1: A neuronal calcium-regulated repressor of the 5-HT1A receptor gene. 1291 78