• Anxiety and mood
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• v.5 no.2
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• pp.75-79
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• 2009

In this article, we review the efficacy of early interventions after traumatic incidents and during acute stress disorder (ASD). There are some evidences that psychopharmacological medications such as propronolol, morphine, and hydrocortisone are effective in the prevention of posttraumatic stress disorder (PTSD). Considering the role of selective serotonin reuptake inhibitors in hippocampal neurogenesis and an animal model of PTSD, early administration of selective serotonin reuptake inhibitors is also fairly promising. Other pharmacological treatments including benzodiazepines did not treat ASD nor prevent PTSD. There are good evidences that cognitive behavioral therapy including cognitive therapy and prolonged exposure is a valuable intervention for ASD and the most effective prevention for PTSD. No contolled researches on eye movement desensitization&reprocessing, psychodynamic psychotherapy and hypnotherapy have performed. Recent randomized controlled studies using psychological debriefing did not prove as a useful intervention for the prevention of PTSD until now, although the efficacy of debriefing has been at the centre of controversy.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.337-343
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• 2010

Long-term potentiation (LTP) and long-term depression (LTD) have both been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. In a previous study, we suggested that a developmental increase in serotonin [5-hydroxytryptamine (5-HT)] might be involved in the decline of LTP, since 5-HT inhibited its induction. In the present study, to further understand the role of 5-HT in a developmental decrease in plasticity, we investigated the effect of 5-HT on the induction of LTD in the pathway from layer 4 to layer 2/3. LTD was inhibited by 5-HT ($10{\mu}M$) in 5-week-old rats. The inhibitory effect was mediated by activation of 5-$HT_2$ receptors. Since 5-HT also regulates the development of visual cortical circuits, we also investigated the role of 5-HT on the development of inhibition. The development of inhibition was retarded by chronic (2 weeks) depletion of endogenous 5-HT in 5-week-old rats, in which LTD was reinstated. These results suggest that 5-HT regulates the induction of LTD directly via activation of 5-$HT_2$ receptors and indirectly by regulating cortical development. Thus, the present study provides significant insight into the roles of 5-HT on the development of visual cortical circuits and on the age-dependent decline of long-term synaptic plasticity.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.54-54
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• 2003

Prostate gland contains neuroendocrine cells (PNECs) are playing important roles in physiological and pathophysiological processes of the prostate gland. Here, we investigated the role of purinoceptors in PNECs freshly isolated from rat ventral prostate (RPNECs) that show immunoreactivity to chromogranin A. Fura-2 ratiometry revealed that ATP evokes both fast Ca$\^$2+/ influx and store Ca$\^$2+/ release in RPNECs. A whole-cell patch clamp study demonstrated fast inactivating cationic current activated by ATP or by ${\alpha}$,${\beta}$-MeATP, which was blocked by ATP-TNP. The activation of P2X inward current was tightly associated with a sharp increase in [Ca$\^$2+/]$\sub$c/. The presence of P2X1/3 subtypes were proved by RT-PCR analysis. For the stored Ca$\^$2+/ release, ATP and UTP showed similar effects, suggesting the dominant role or P2Y2 subtypes, also confirmed by RT-PCR. Both P2X (${\alpha}$,${\beta}$-MeATP) and P2Y (UTP) stimulation induced changes in the cell morphology (initial shrinkage and blob formation on the surface) reversibly. Exocytotic membrane trafficking events were monitored with the membrane-bound fluorescent dye, FM1-43 using confocal microscopy. In spite of the similar Ca$\^$2+/ responses, UTP was far less effective in triggering exocytosis than ${\alpha}$,${\beta}$ -MeATP. Since serotonin is reportedly stored in the secretory granule of PNECs, we directly examined whether the aforementioned agonists elicit release of serotonin using carbon fiber electrode-amperometry. In accordance with the results of FM1 -43 experiments, ${\alpha}$,${\beta}$-MeATP efficiently evoke serotonin secretion while not with UTP. In summary, the P2X-mediated Ca$\^$2+/ influx plays crucial roles in the exocytosis of RPNECs. Although a global increase in [Ca$\^$2+]$\sub$c/ might be related with the morphological changes, a sharp rise of [Ca$\^$2+/]$\sub$c/ in the putative sub-plasmalemmal ‘microdomains’ might be a decisive factor for the exocytosis.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.17-29
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• 1988

The author examined the effects of lidocaine on the veratrine-or potassium-induced release of neurotransmitters to determine the possible role of amino acid neurotransmitters in lidocaine-induced convulsion. The examined transmitters were gamma-aminobutyric acid (GABA), aspartic acid, glutamic acid and norepinephrine which are released from the synaptosomes. Furthermore, the effects of lidocaine on the binding to receptors and synaptosomal uptake of the two transmitters, GABA and glutamic acid, were determined in crude synaptic membranes and synaptosomes. In addition, the effects of propranolol, norepinephrine and serotonin on the release of amino acid neurotransmitters were also examined. The veratrine-induced release of GABA was most severely inhibited by lidocaine and propranolol, while norepinephrine and serotonin reduced the release of aspartic acid and glutamic acid more than the GABA release. Generally the potassium-induced release was much more resistant to the lidocaine action than the veratrine-induced release. Among the neurotransmitters examined, the aspartic acid release was most prone to the lidocaine action, while the GABA release was most resistant. Concentrations of lidocaine below 1 mM did not significantly change the GABA and glutamic acid receptor binding and uptake. These results indicate that the blocking of sodium channels by lidocaine can result in the selective depression of the GABA release. This may result in unlimited excitation of the central nervous system.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.12 no.2
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• pp.165-178
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• 2001

In order to elucidate the biological etiology and the relationship between the ontogenesis of serotonin system and psychopathology in ADHD, plasma serotonin(5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) were measured and the correlation between the plasma levels of 5-HT and 5-HIAA and age were evaluated in 46 ADHD patients and 18 control subjects. The ADHD patients were composed of 16 combined type, 10 inattentive type, and 20 hyperactive-impulsive type and the control subjects were communication disorders. The results are summarized as follows：1) There was significant difference in plasma 5-HT levels among combined, inattentive and hyperactive-impulsive and control subjects(ANOVA F=4.33, df 3, 60, p<0.05), and post-hoc test using Scheffe method showed significant difference between the combined type and control group. But, post-hoc tests showed no significant differences between combined and inattentive, combined and hyperactive-impulsive, hyperactive-impulsive and inattentive, hyperactive-impulsive and control and inattentive and control groups. 2) There was no significant differences in plasma 5-HIAA levels among the combined, hyperactive- impulsive, inattentive and control groups(ANOVA F=2.08, df 3, 60, p>0.05). 3) Significant difference in 5-HT level was found between the whole ADHD group(N=46) and the control group(N=18)(T=3.10, df 62, p<0.05). But no significant difference in 5-HIAA level was found between the whole ADHD group and the control group(T=1.90, df 62, p>0.05). 4) Plasma 5-HT and 5-HIAA levels showed no significant correlation with TOVA findings(5-HT：omission pearson correlation 0.10, commision 0.23, reaction time 0.01, variability in attention 0.11, all p>0.05, 5-HIAA：omission 0.21, commision 0.15, reaction time 0.09, variability in attention 0.15, all p>0.05). 5) Plasma 5-HT and 5-HIAA levels showed no significant correlation with attention, hyperactivity and impulsivity based on DSM-IV criteria. 6) Plasma 5-HT and 5-HIAA levels showed no significant correlation with age both in ADHD and control group. These findings show that decreased plasma 5-HT level may play a role in the genesis of ADHD, but this finding has no significant correlation with the psychopathology of ADHD. And we could not find any significant differences in ontogenetic processes in 5-HT. Future studies should be focused on the drug effects, family history and prognosis based on the biochemical subtypes(high and low 5-HT group).

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.7 no.1
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• pp.77-91
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• 1996

In order to elucidate the biological etiology and the effects of comorbidity on biological variables in tic disorders, plasma serotonin (5-hydroxlfryptamine, 5-HT) and 5-hydroxy- indoleacetic acid (5-HIAA) we.e measured in 87 tic disorders and 30 control subjects. The 87 tic disorder were composed of 45 Tourette's disorder(TS), 22 chronic motor tic disorders (CMT) and 20 transient tic disorders (TTD). Among these patients,43 patients were pure tic disorder (PT), 28 subject also had attention deficit hyperactivity disorder (T+ADHD) and 16 subjects had obsessive compulsive disorders (T+ OCD) as comorbid disorders. The results are summarized as follows : 1) Plasma 5-HT levels showed significant positive correlations with plasma 5-HIAA levels (Pennon r=0.77, p<0.05). 2) Plasma 5-HT and 5-HIAA levels showed no significant correlation with age in tic disorders. 3) Plasma 5-HIAA and 5-HT levels showed no significant correlations with age in control subjects. 4) There was significant difference in plasma 5-HT levels among TS, CMT, TTD and control groups (ANOVA F=34.48, df=3, 113, p<0.01), and post-hoc test using Scheffe method showed significant differences between control and TS, control and CMT, control and ITD groups. But, post-hoc test showed no significant differences between TS and CMT, TS and TTD, CMT and TTD groups. 5) There was significant difference in plasma 5-HIAA levels among TS, CMT, TTD and control groups (ANOVA F=26.48, df=3, 113, p<0.01), and post-hoc test using Scheffe method showed significant differences between control and TS, control and CMT, control and TTD groups. But, post-hoc test showed no significant differences between TS and CMT, TS and TTD, CMT and TID groups.f) There was significant difference in plasma 5-HT and 5-HIAA levels among PT, T+ADHD, T+OCD and contol groups (ANOVA 5-HT, F=37.59, df=3, 113, p<0.01, 5-HIAA, F=27.37, df=3, 113, p<0.01), and post-hoc test using Scheffe method showed signiscant differences between control and PT, control and T+ADHD and control and T+OCB. But, post-hoc test showed no significant differences between PT and T+ADHD, PT and T+ OCD and T+ADHD and T+ OCD. These results show that decreased 5-HT and 5-HIAA levels may play a role in the genesis of tic disorders, but these findings have no significant correlations with the severity of tic disorders. And the comorbid disorders of tics may have minimal effects on the biochemical abnormalities. Future studies must be focused on the effects of serotonin agonists and antagonists on tic disorders and molecular biological methodology may enhance to elucidate the mechanisms of these abnormal findings.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.65-70
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• 2012

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-weekold rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-$HT_2$ receptors, but not by the activation of either 5-$HT_{1A}$ or 5-$HT_3$ receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.149-153
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• 2005

The aim of the present study was to determine whether serotonergic drugs could reverse lipopolysaccharide (LPS)-induced anorexia in rats. LPS ($500{\mu}g$/kg body weight) and all serotonergic drugs, except for 8-OH-DPAT (subcutaneous), were injected intraperitoneally into Sprague-Dawley rats. Without the LPS injection, 8-OH-DPAT (1A agonist), metergoline (1/2 antagonist), and mianserin (2A/2C antagonist) exerted no effects on food intake at any of the doses tested, but ketanserin (2A antagonist) caused an increase of food intake at 4 mg/kg. RS-102221 (2C antagonist) reduced food intake at 2 and 4 mg/kg. LPS reduced food intake 1 hour after injection, and food intake remained low until the end of measurement period (24 hours) (p<0.05). Pretreatment of rats with 8-OH-DPAT partially recovered of cumulative food intake at all measured times (2, 4, 6, 8, and 24 hours after LPS injection). Pretreatment with metergoline resulted in a partial recovery of cumulative food intake at 2, 4, 6, and 8 hours, but not at 24 hours. Ketanserin caused partial recovery at 2 and 4 hours only. Mianserin and RS-102221 had no effects on LPS-reduced food intake. A variety of serotonergic drugs ameliorated anorexic symptoms, which suggesting that the serotonin system plays a role in LPS-induced anorexia.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.517-527
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• 2020

Layer 2/3 pyramidal neurons (L2/3 PyNs) of the cortex extend their basal dendrites near the soma and as apical dendritic tufts in layer 1, which mainly receive feedforward and feedback inputs, respectively. It is suggested that neuromodulators such as serotonin and acetylcholine may regulate the information flow between brain structures depending on the brain state. However, little is known about the dendritic compartment-specific induction of synaptic transmission in single PyNs. Here, we studied layer-specific serotonergic and cholinergic induction of long-term synaptic plasticity in L2/3 PyNs of the agranular insular cortex, a lateral component of the orbitofrontal cortex. Using FM1-43 dye unloading, we verified that local electrical stimulation to layers 1 (L1) and 3 (L3) activated axon terminals mostly located in L1 and perisomatic area (L2/3). Independent and AMPA receptor-mediated excitatory postsynaptic potential was evoked by local electrical stimulation of either L1 or L3. Application of serotonin (5-HT, 10 μM) induced activity-dependent longterm depression (LTD) in L2/3 but not in L1 inputs. LTD induced by 5-HT was blocked by the 5-HT₂ receptor antagonist ketanserin, an NMDA receptor antagonist and by intracellular Ca²⁺ chelation. The 5-HT₂ receptor agonist α-me-5-HT mimicked the LTD induced by 5-HT. However, the application of carbachol induced muscarinic receptor-dependent LTD in both inputs. The differential layer-specific induction of LTD by neuromodulators might play an important role in information processing mechanism of the prefrontal cortex.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.71-80
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• 2018

In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to high-frequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an $IC_{50}$ value of $9.43{\mu}M$ and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding ($k_{+1}$) and unbinding ($k_{-1}$) rate constants for the paroxetine effect were $4.5{\mu}M^{-1}s^{-1}$ and $35.8s^{-1}$, respectively, yielding a calculated $K_D$ value of $7.9{\mu}M$. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a use-dependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.