Growing evidence indicates that the serotonin system is important in learning and memory. In particular, several preclinical and clinical studies suggest that modulating the 5-HT1A receptor can influence learning and memory, and indeed, it has been observed that presynaptic 5-HT1A receptor agonists and postsynaptic 5-HT1A receptor antagonists tend to ameliorate the learning/memory impairment induced by various methods. In contrast, post-synaptic 5-HT1A receptor agonists tend to decrease the learning/memory function. These observations suggest the possibility that modulating neurotransmission mediated by the 5-HT1A receptor may be effective as a therapeutic strategy for enhancing learning and memory in various neuropsychiatric disorders. Unfortunately, there is no available discussion on the relationship between 5-HT1A receptor and learning/memory in Korea. This article reviews the clinical or preclinical literature on this issue.
Korea ; Learning* ; Memory* ; Receptor, Serotonin, 5-HT1A* ; Serotonin ; Synaptic Transmission

BACKGROUND: Spinal 5-hydroxytryptamine (5-HT) has been shown to display an antinociceptive effect, which is mediated by 5-HT receptors. Previous studies have revealed the presence of at least four types of 5-HT receptors in the spinal cord. The aim of this study was to assess the role of each spinal 5-HT receptor in the antinociception of intrathecal 5-HT using the formalin test. METHODS: Rats were implanted with lumbar intrathecal catheters. After the administration of 5-HT, formalin-induced nociceptive behavior (flinching response) was observed for 60 min. To further clarify the role of the 5-HT receptors in the antinociception of 5-HT, several antagonists of 5-HT receptors were administered intrathecally 10 min before 5-HT delivery, and formalin was injected 10 min later. RESULTS: Intrathecal 5-HT dose-dependently suppressed flinching during phase 1 and 2 in the formalin test. 5-HT1B (GR 55562), 5-HT2C (N-desmethylclozapine), 5-HT3 (LY-278,584) and 5-HT4 (SDZ-205,557) receptors antagonists reversed this antinociception by 5-HT during both phases in the formalin test. 5-HT1A receptor antagonist (WAY-100635) decreased antinociception by 5-HT in phase 2, but not in phase 1. A 5-HT1D receptor antagonist (BRL 15572) did not antagonize the antinociception of 5-HT in either phases. CONCLUSIONS: Spinal 5-HT1B, 5-HT2C, 5-HT3 and 5-HT4 receptors, but not the 5-HT1D receptor, are involved in the antinociception of serotonin in the facilitated state and in the acute pain evoked by a formalin stimulus. The 5-HT1A receptor seems to play a role in 5-HT-induced antinociception in the facilitated state.
Acute Pain ; Animals ; Catheters ; Formaldehyde ; Pain Measurement ; Rats* ; Receptor, Serotonin, 5-HT1A ; Receptor, Serotonin, 5-HT1D ; Receptors, Serotonin ; Receptors, Serotonin, 5-HT4 ; Serotonin* ; Spinal Cord*

We tried to review and update clinical and preclinical studies evaluating vilazodone's role as an antidepressant for patients with major depressive disorder (MDD). In terms of its mechanism of actions, we sought to elaborate them mainly through preclinical animal studies. A data search was conducted in November 1, 2013, using the key terms "vilazodone" or "Viibryd," in PubMed and Medline databases. All published and unpublished studies are included and citations from publications were also reviewed for additional references. Five unpublished, phase-II and two pivotal published phase-III clinical trials with nearly identical design (8-week, double-blind, randomized, and placebo-controlled) investigated efficacy of vilazodone, were found for the treatment of patients with MDD. Two post-hoc studies and one long-term open study were also included. Data were thoroughly reviewed to incorporate the pharmacology, action mechanism, efficacy and safety for the vilazodone in the treatment of major depressive disorder. Vilazodone is an antidepressant with novel mechanism of action because its chemical structure is unrelated to conventional antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist profile. Vilazodone is an effective and safe treatment option with its novel action mechanisms for patients with depression. Its putative benefits compared with other antidepressants must be thoroughly studied in adequately-powered and well-designed future clinical trials.
Animals ; Antidepressive Agents ; Depression ; Depressive Disorder, Major* ; Humans ; Pharmacology ; Receptor, Serotonin, 5-HT1A ; Serotonin ; Vilazodone Hydrochloride

OBJECTIVE: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. METHODS: One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). RESULTS: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. CONCLUSION: Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.
Antidepressive Agents ; Counseling ; Depression ; Depressive Disorder, Major ; Genotype ; Humans ; Psychotherapy ; Receptor, Serotonin, 5-HT1A ; Receptor, Serotonin, 5-HT2A ; Serotonin ; Serotonin Plasma Membrane Transport Proteins

The role of 5-hydroxytryptamine (5-HT)1A receptor activity in prenatal ischemia was studied, by injecting 8-hydroxy-dipropylaminotetraline (8-OH-DPAT; 50 microgram/kg, s.c.), a 5-HT1A agonist on gestation day 17, and 30 min later inducing transient ischemia by ligating the uterine vessels for 30 min. On postnatal day 95, rats that had experienced prenatal ischemia showed impaired motor coordination and reduced concentration of 5-HT in the cerebellum compared with Sham-operated controls. In addition, they showed increased 5-HT1A receptor densities in the cerebral cortex. Pretreatment with 8-OH-DPAT ameliorated the behavioral and neurochemical sequelae measured in the present study. The results suggest that 5-HT1A receptors protect the brain from ischemic insult and/or facilitate recovery after prenatally experienced ischemia.
8-Hydroxy-2-(di-n-propylamino)tetralin* ; Animals ; Brain ; Cerebellum ; Cerebral Cortex ; Ischemia* ; Neuroprotective Agents* ; Pregnancy ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin ; Serotonin 5-HT1 Receptor Agonists

OBJECTIVE: Interest in the "at-risk mental state" (ARMS) for psychosis has increased because early intervention is expected to delay or prevent the onset of schizophrenia. However, the optimum intervention strategy remains controversial, especially with regard to antipsychotics. Although administration of antipsychotic medications is often associated with adverse effects and raises ethical considerations, recent studies have shown that some novel antipsychotics are safer and more tolerable for young people than conventional antipsychotics. We investigated whether administration of perospirone, a combined serotonin (5-HT)/dopamine antagonist and 5-HT1A receptor agonist, could alleviate prodromal symptoms and be well tolerated by clinical high risk patients. METHODS: The participants were outpatients seeking help. The Structured Interview for Prodromal Symptoms was performed in patients identified as being at clinical high risk. The Scale of Prodromal Symptoms (SOPS) was also completed and changes of subjective experience were assessed with the Subjective Well-being under Neuroleptics, short version. The incidence of akathisia was recorded by using the Barnes Akathisia Scale. Subjects were monitored for 26 weeks after starting medication. RESULTS: SOPS scores improved significantly after 26 weeks of perospirone therapy, while BAS scores did not show deterioration. No serious adverse events occurred during the study. CONCLUSION: This trial suggests that perospirone therapy provides a clinical benefit for clinical high risk subjects without causing serious adverse events. Although further placebo-controlled studies are needed for confirmation, perospirone might be one of optimum treatments for individuals at imminent risk of psychosis.
Antipsychotic Agents ; Early Intervention (Education) ; Humans ; Incidence ; Outpatients ; Prodromal Symptoms ; Psychomotor Agitation ; Psychotic Disorders ; Receptor, Serotonin, 5-HT1A ; Schizophrenia ; Serotonin

OBJECTIVE: Serotonergic dysfunction is quite evident in panic disorder. We investigated whether the C(-1019)G polymorphism of 5-HT1A receptor gene may play a role in the pathogenesis of panic disorder in a Korean population. METHODS: The 5-HT1A receptor genotype for the single nucleotide polymorphism (SNP) C(-1019)G was analyzed in 94 patients and 111 healthy controls. The severity of the patients' symptoms was examined using the Spielberger State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale (PDSS), Anxiety sensitivity index (ASI), Acute Panic Inventory (API) and Hamilton's Rating Scale for Anxiety (HAM-A). RESULTS: The distribution of the genotypes of the C/G polymorphism did not differ significantly from those predicted by Hardy-Weinberg equilibrium in patients as well as the controls. No association between the C(-1019)G polymorphism and panic disorder was detected in either the allele frequency or genotype distribution. There was no significant association with genotype distribution in the panic disorder with agoraphobia. However, there was a significant difference of symptom severity between C/C, C/G, and G/G genotype or between C and G allele in panic disorder patients without agoraphobia. PDSS scores were significantly higher in subjects with the G/G genotype or with G allele in patients without agoraphobia, not in total patients or patients with agoraphobia. CONCLUSION: Although there were no significant differences in the genotype and allele distributions, we found a significant association between panic symptom severity and the serotonin 1A receptor gene. This result suggests that the serotonin 1A receptor and serotonin may play a role in the pathogenesis of panic disorder.
Agoraphobia ; Alleles ; Anxiety ; Gene Frequency ; Genotype ; Humans ; Panic ; Panic Disorder ; Polymorphism, Single Nucleotide ; Receptor, Serotonin, 5-HT1A ; Serotonin

Developmental disability shows life-long behavioral abnormality with no significant physical malformation. This study was undertaken to develop an animal model for developmental disability by using two-factor approach. Lipopolysaccharide (LPS), a bacterial toxin, and NAN-190, a 5-HT1A receptor antagonist, were administered to Sprague-Dawley rats on postnatal day (PND) 5 to induce inflammation and an altered 5-HT system, respectively. Long-term alteration of behavior occurred in the drug-treated groups. The LPS-treated group showed impaired motor coordination in the Rota-rod test. The LPS- treated or both LPS and NAN-190-treated groups showed impaired fore-paw muscle power in the wire maneuver test. These groups also showed decreased white matter volume and increased serotonergic fibers. The LPS and NAN-190-treated group also exhibited neurologic deficit in the placing reaction test and impaired equilibrium function in the tilt table test. The results showed that a variety of altered behaviors can be generated by two factor model, and suggested that combination of important etiologic factors and possible underlying defects is a promising strategy of establishing an animal model for developmental disabilities.
Animals* ; Developmental Disabilities* ; Inflammation ; Models, Animal* ; Neurologic Manifestations ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A ; Serotonin* ; Tilt-Table Test

OBJECTIVETo assess whether HTR1A and HTR1B polymorphisms are associated with the predisposition, gender, PUMC Classification and/or severity of adolescent idiopathic scoliosis (AIS).

METHODSRs6294 (HTR1A) and rs6296 (HTR1B) were genotyped in 103 AIS patients treated from January 2006 to March 2007, and 108 controls with matched gender and age. The data were analyzed by the allelic and genotypic association analysis, and the genotype-phenotype (gender, PUMC Classification, and Cobb angle) association analysis.

RESULTSThe distributions of the alleles of all the 2 SNPs met Hardy-Weinberg equilibrium in the controls (goodness-of-fit chi(2) test, P > 0.05). The allele A of rs6294 was related with the occurrence of AIS (P = 0.041), but differences of the allele frequencies of rs6296 and the genotype frequencies of both SNPs between 2 groups had no statistical significance (P > 0.05). The genotype A/A + A/G of rs6294 was associated with AIS PUMC type III, and there was no other positive results in genotype-phenotype association analysis.

CONCLUSIONThese results suggest that HTR1A may be a predisposition gene of AIS PUMC type III, and PUMC Classification may has its genetic basis.

Adolescent ; Gene Frequency ; Genetic Association Studies ; Genotype ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptor, Serotonin, 5-HT1A ; genetics ; Receptor, Serotonin, 5-HT1B ; genetics ; Scoliosis ; genetics

Tardive dyskinesia is characterized by choreiform movements, or rhythmic abnormal involuntary movements of the face, mouth, tongue, trunk, and limbs. It is frequently associated with the use of neuroleptic medications. The choreiform movements are irreversible in some patients, even after the drug is withdrawn. Although no reliable treatment for tardive dyskinesia exists, atypical antipsychotics are associated with a significantly lower incidence of tardive dyskinesia than typical antipsychotics. Moreover, recent reports suggest that atypical antipsychotics may have a beneficial effect on tardive dyskinesia remission. Until recently, evidence for the effectiveness of aripiprazole on tardive dyskinesia has been mixed. Aripiprazole has a unique mechanism of action and has various effects in tardive dyskinesia. The drug acts as a partial D2 receptor agonist that can stabilize D2 up-regulation, and as a partial 5-HT1A receptor agonist and a 5-HT2A receptor antagonist, and can increase the release of dopamine in the striatum.
Antipsychotic Agents ; Chorea ; Dopamine ; Dyskinesias ; Extremities ; Humans ; Incidence ; Mouth ; Movement Disorders ; Piperazines ; Quinolones ; Receptor, Serotonin, 5-HT1A ; Receptor, Serotonin, 5-HT2A ; Tongue ; Up-Regulation ; Aripiprazole