Creation, effects on embryo quality, and clinical outcomes of a new embryo culture medium with 31 optimized components derived from human oviduct fluid: A prospective multicenter randomized trial.

Purpose: Our aim is to make an ideal embryo culture medium close to human oviduct fluid (HOF) components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT). Methods: Study I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium "HiGROW OVIT®" (OVIT) was designed. Study II: Embryos (2 pronuclei (2PN) = 9633) were assigned from 1435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo-preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT. Results: The novel medium 'OVIT' was produced according to 31 HOF components. The concentrations of essential amino acids (e-AAs) were lower in OVIT than in current media, yet the opposite was true for ne-AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group. Conclusions: The novel medium 'OVIT' was produced according to HOF data. The OVIT had significantly better embryo quality and clinical outcomes than the current media.

Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas.

STUDY QUESTION: How does progesterone alter matrix remodeling in abdominal wall endometriomas compared with normal endometrium? SUMMARY ANSWER: Progesterone may prevent attachment of endometrial cells to the abdominal wall, but does not ameliorate abnormal stromal cell responses of abdominal wall endometriomas. WHAT IS KNOWN ALREADY: Menstruation is a tightly orchestrated physiologic event in which steroid hormones and inflammatory cells cooperatively initiate shedding of the endometrium. Abdominal wall endometriomas represent a unique form of endometriosis in which endometrial cells inoculate fascia or dermis at the time of obstetrical or gynecologic surgery. Invasion of endometrium into ectopic sites requires matrix metalloproteinases (MMPs) for tissue remodeling but endometrium is not shed externally. STUDY DESIGN SIZE, DURATION: Observational study in 14 cases and 19 controls. PARTICIPANTS /MATERIALS, SETTING, METHODS: Tissues and stromal cells isolated from 14 abdominal wall endometriomas were compared with 19 normal cycling endometrium using immunohistochemistry, quantitative PCR, gelatin zymography and cell attachment assays. P values < 0.05 were considered significant and experiments were repeated in at least three different cell preps to provide scientific rigor to the conclusions. MAIN RESULTS AND THE ROLE OF CHANCE: The results indicate that MMP2 and MMP9 are not increased by TGFß1 in endometrioma stromal cells. Although progesterone prevents attachment of endometrioma cells to matrix components of the abdominal wall, it does not ameliorate these abnormal stromal cell responses to TGFß1. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Endometriomas were collected from women identified pre-operatively. Not all endometriomas were collected. Stromal cells from normal endometrium were from different patients, not women undergoing endometrioma resection. WIDER IMPLICATIONS OF THE FINDINGS: This work provides insight into the mechanisms by which progesterone may prevent abdominal wall endometriomas but, once established, are refractory to progesterone treatment. STUDY FUNDING/COMPETING INTEREST(S): Tissue acquisition was supported by NIH P01HD087150. Authors have no competing interests.

Olfactory deficits in individuals at risk for psychosis and patients with schizophrenia: relationship with socio-cognitive functions and symptom severity.

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis.

Possible relation between olfaction and anxiety in healthy subjects.

AIMS: While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects. METHODS: We investigated the effect of state and trait anxiety on the detection and recognition thresholds for five different odors in 124 healthy subjects (62 men and 62 women, mean age = 27.2 years) using a T&T olfactometer. RESULTS: While the influences of age, socioeconomic status, IQ, and smoking history on olfaction were not significant, women had a lower recognition threshold for the odor of sweet fruit and a higher detection threshold for that of rotten food as compared with men. Both state and trait anxiety ratings were significantly associated with reduced olfactory ability, especially for identification of rose odor. CONCLUSIONS: These findings suggest that emotional status affects olfactory functioning in healthy subjects. Our findings may also partly explain the mild olfactory impairment reported in clinical conditions, such as anxiety disorders.

Neonatal exposure to MK-801 reduces mRNA expression of mGlu3 receptors in the medial prefrontal cortex of adolescent rats.

Schizophrenia is considered as a "neurodegenerative" and "neurodevelopmental" disorder, the pathophysiology of which may include hypofunction of the N-methyl-D-aspartate receptor (NMDA-R) or subsequent pathways. Accordingly, administration of NMDA-R antagonists to rodents during the perinatal period may emulate some core pathophysiological aspects of schizophrenia. The effect of 4-day (postnatal day; PD 7-10) administration of MK-801, a selective NMDA-R antagonist, on gene expression in the medial prefrontal cortex (mPFC), hippocampus, and amygdala was evaluated using quantitative polymerase chain reaction methods. Specifically, we sought to determine whether genes related to Glu transmissions, for example those encoding for NMDA-Rs, metabotropic Glu receptors (mGluRs), or Glu transporters, were altered by neonatal treatment with MK-801. Model rats showed downregulation of the mGluR3 subtype in the mPFC around puberty, especially at PD 35 in response to MK-801 or during ontogenesis without pharmacological manipulations. Genes encoding for other mGluRs subtypes, that is NMDA-Rs and Glu transporters, were not affected by the neonatal insult. These results suggest that NMDA-R antagonism in the early course of development modulates the expression of mGluR3 in mPFC around puberty. Thus, mGluR3 may serve as a potential target to prevent the onset and progression of schizophrenia.

Relationships between erythrocyte membrane mono- and poly- unsaturated fatty acid composition and clinical/cognitive indices in antipsychotic-free schizophrenia patients.

Introduction: Membrane phospholipid abnormalities are considered a pathophysiological background for schizophrenia. The aim of the study was to explore in detail the fatty acid (FA) composition in patients with antipsychotic-free schizophrenia and its association with clinical symptoms and cognitive function. Materials and methods: Erythrocyte membrane FAs were measured in 29 antipsychotic-free patients with schizophrenia (male/female = 11/18; mean [standard deviation] age=26.7 [7.9] years) and age and sex-matched 32 healthy volunteers. Clinical symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), and the Schizophrenia Cognition Rating Scale (SCoRS). Results: Eicosapentaenoic acid levels were lower in the schizophrenia group than in the healthy control group. In contrast, arachidonic acid and nervonic acid levels were higher in the schizophrenia group than in the control group. Nervonic acid levels were significantly associated with depression scores as measured by the PANSS. No FA levels were correlated with BACS score; however, oleic acid levels were significantly related to cognitive dysfunction, as measured by the SCoRS. Conclusion: These findings suggest that depressive symptoms along with cognitive dysfunction in daily living in schizophrenia may be linked to the FA composition abnormalities. Further studies will be needed to examine potential longitudinal FA changes during the course of schizophrenia as well as disease specificity.

Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.

Introduction: Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). Materials and methods: This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Results: Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). Discussion: The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

Effect of transient blockade of N-methyl-D-aspartate receptors at neonatal stage on stress-induced lactate metabolism in the medial prefrontal cortex of adult rats: role of 5-HT1A receptor agonism.

Decreased activity of the medial prefrontal cortex (mPFC) has been considered a basis for core symptoms of schizophrenia, an illness associated with a neurodevelopmental origin. Evidence from preclinical and clinical studies indicates that serotonin (5-HT)1A receptors play a crucial role in the energy metabolism of the mPFC. This study was undertaken to determine (1) if transient blockade of N-methyl-D-aspartate receptors during the neonatal stage inhibit energy demands in response to stress, as measured by extracellular lactate concentrations, in the mPFC at the young adult stage, and (2) if tandospirone, a 5-HT1A partial agonist, reverses the effect of the neonatal insult on energy metabolism. Male pups received MK-801 (0.20 mg/kg) on postnatal days (PDs) 7-10. On PD 63, footshock stress-induced lactate levels were measured using in vivo microdialysis technique. Tandospirone (0.1, 1.0, and 5.0 mg/kg) was administered once daily for 14 days before the measurement of lactate levels. Neonatal MK-801 treatment suppressed footshock stress-induced lactate production in the mPFC, but not caudate-putamen, whereas basal lactate levels were not significantly changed in either brain region. The MK-801-induced suppression of footshock stress-induced lactate production in the mPFC was attenuated by tandospirone at 1.0mg/kg/day, but not 0.1 or 5.0 mg/kg/day, which is an effect antagonized by coadministration of WAY-100635, a selective 5-HT1A antagonist. These results suggest a role for impaired lactate metabolism in some of the core symptoms of schizophrenia, for example, negative symptoms and cognitive deficits. The implications for the ability of 5-HT1A agonism to ameliorate impaired lactate production in the mPFC of this animal model are discussed.

Apocynin-Tandospirone Derivatives Suppress Methamphetamine-Induced Hyperlocomotion in Rats with Neonatal Exposure to Dizocilpine.

Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.

Membrane fatty acid levels as a predictor of treatment response in chronic schizophrenia.

Abnormal fatty acid composition in neural membranes, that is, the balance between essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has been suggested to be related to the psychotic symptoms and cognitive impairment of schizophrenia. This study was conducted to test the hypothesis that the ability of atypical antipsychotic drugs to ameliorate positive symptoms and cognitive function relevant to daily living would be predicted by baseline EPUFAs concentrations in the erythrocyte membrane in subjects with schizophrenia. A total of 24 actively psychotic patients with schizophrenia participated in the study. After blood drawing, they were treated with olanzapine or perospirone. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative symptoms (SANS), as well as the script tasks, a measure of event schema recognition, were administered at baseline and 3months after the start of treatment. Erythrocyte membrane fatty acid levels were analysed using a gas chromatography system. Scores of SAPS and SANS, as well as script task performance, were improved during treatment with either antipsychotic drug. Regression analysis indicates baseline EPUFAs concentrations were positively and negatively related with percent improvement of positive symptoms and script task performance, respectively. The results of this study suggest composition of phospholipids in the erythrocyte membrane provide a feasible marker to predict treatment response in patients with schizophrenia.

Change in the expression of myelination/oligodendrocyte-related genes during puberty in the rat brain.

Age-dependent changes of gene expression in the prefrontal cortex (PFC) of rats around the time of puberty were investigated by means of microarray and quantitative polymerase chain reaction (qPCR). About 127 and 138 genes were increased and decreased, respectively, in the PFC of rats at post-puberty (PD56) compared with those at pre-puberty (PD35). Functional analysis showed significant associations of these genes with aging, cellular development, and neuropsychological disorders. qPCR analysis confirmed down-regulation of seven genes related to myelination. As these genes have been reported to be diminished in the brain of patients with schizophrenia, the results of this study suggest an exaggerated maturation process may contribute to the pathogenesis of psychotic disorders.

Association between olfactory sulcus morphology and olfactory functioning in schizophrenia and psychosis high-risk status.

Olfactory impairment has been reported in patients with schizophrenia and individuals with a high risk of psychosis, but its neural basis is largely unknown. We used magnetic resonance imaging to investigate the morphology of the olfactory sulcus (an indicator of olfactory system development) and its relation to olfactory function in 38 persons with an at-risk mental state (ARMS), 62 patients with schizophrenia, and 61 healthy controls. Odor detection and identification were examined with a T & T olfactometer. Compared with the controls, the olfactory sulcus was significantly shallower and odor identification was inferior among the ARMS and schizophrenia subjects. Across all subjects, but not within each group, the olfactory sulcus depth was significantly related to better identification of odors. Our results support the concept that olfactory sulcus morphology reflects the neurodevelopmental process of the olfactory system.

T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating.

RATIONALE: Neurodegenerative changes have been suggested to provide a basis for the pathophysiology of schizophrenia. T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl} azetidin-3-ol maleate) is a novel compound with neuroprotective and neurite-outgrowth effects, as elicited in rat primary cultured neurons. OBJECTIVES: We examined the effect of T-817MA on phencyclidine (PCP)-induced disruption of prepulse inhibition (PPI), a measure of sensorimotor gating, in male Wistar rats. MATERIALS AND METHODS: In chronic experiments, male Wistar rats were injected intermittently with PCP (2.0 mg/kg, i.p., three times per week) or vehicle (saline, 2.0 ml/kg) for 1 month. T-817MA (0.21 or 0.07 mg/ml, p.o.) or distilled water was administered throughout the study period. In an acute experiment, T-817MA (8.4 mg/kg, p.o.) or distilled water was administered, followed by treatment with PCP (2.0 mg/kg, i.p.) or vehicle (saline, 2.0 ml/kg), before PPI measurements. RESULTS: Intermittent administration of PCP for 1 month induced persistent disruption of PPI. Coadministration of T-817MA at 0.21 mg/ml but not 0.07 mg/ml completely blocked PCP-induced disruption of PPI, whereas T-817MA (0.21 mg/ml) by itself did not show a significant effect on PPI in control rats. On the other hand, single administration of T-817MA did not affect PPI disruption by acute treatment with PCP. CONCLUSIONS: These results suggest that T-817MA is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions. Our findings provide a novel therapeutic approach for patients with schizophrenia.

Blazein of a new steroid isolated from Agaricus blazei Murrill (himematsutake) induces cell death and morphological change indicative of apoptotic chromatin condensation in human lung cancer LU99 and stomach cancer KATO III cells.

Blazein was isolated from mushroom (Agaricus blazei Murrill) and identified by Mass and 1H-NMR as blazein. The effect of blazein on the DNA of human various cancer cells was investigated. DNA fragmentations by blazein to oligonucreosomal-sized fragments, a characteristic of apoptosis, were observed in the human lung LU99 and stomach KATO III cancer cells. The DNA fragmentations by blazein were observed from day 2 (KATO III cells) or day 3 (LU99 cells) after the addition of blazein to the culture cells. These findings suggest that growth inhibition by blazein results from the induction of apoptosis by the compound.

Essential polyunsaturated fatty acids and social cognition in schizophrenia.

Abnormal metabolism of essential polyunsaturated fatty acids (EPUFAs), a component of phospholipids in neural membranes, has been suggested to be related to the pathophysiology of schizophrenia. The purpose of this study was to examine the relationship between EPUFA concentrations in erythrocyte membranes, a peripheral measure of phospholipid composition in the brain, and clinical variables, such as cognitive performance relevant to social functions, in patients with schizophrenia. Erythrocyte membrane levels of EPUFAs, saturated fatty acids, and monounsaturated acids were measured in 25 patients with schizophrenia and 32 age- and gender-matched 32 normal volunteers. The script tasks, a measure of social cognition, and the Brief Psychiatric Rating Scale were administered to the patients. The levels of EPUFAs, but not those of saturated or monosaturated fatty acids, were significantly lower in patients than in normal controls. The degree of a decrease in EPUFA levels was positively correlated with severity of positive symptoms and impairment of frequency judgment performance on the script tasks, while no such correlations were found with negative symptoms, attention as measured by the Wechsler Adult Intelligence Scale-Revised-Digit Span, or verbal memory as measured by the Auditory Verbal Learning Test. These results provide the first suggestion for a contribution of decreased levels of EPUFAs to impaired social cognition, as represented by event schema, in patients with schizophrenia.

Lactate production and neurotransmitters; evidence from microdialysis studies.

Recent studies have found that lactate metabolism plays a significant role in energy supply during acute neural activation in the brain. We will review evidence from microdialysis studies for a relationship between neurotransmitters and lactate production, as revealed in studies of the effects of psychotropic drugs on stress-induced enhancement of extracellular lactate concentrations. Glutamate enhances stress-induced lactate production via activation of N-methyl-D-asparate receptors, and is affected by uptake of glutamate through glutamate transporters. Findings from microdialysis studies suggest that major neurotransmitters, including norepinephrine, dopamine, serotonin, and GABA (via benzodiazepine-receptors) affect lactate production, depending on brain areas, especially during stress. Among these neurotransmitters, glutamate may principally contribute to the regulation of lactate production, with other neurotransmitter systems affecting the extracellular lactate levels in a glutamate-mediated manner. The role for anaerobic metabolism in the supply of energy, as represented by lactate dynamics, deserves further clarification. Monitoring with intracerebral microdialysis is a reliable method for this purpose. Research into this area is likely to provide a novel insight into the mode of action of psychotropic drugs, and the pathophysiology of some of the stress-related mental disorders as well.

Role of glutamate transporters in the modulation of stress-induced lactate metabolism in the rat brain.

RATIONALE: Lactate, like glucose, has recently been found to be an energy substrate for neural activity. It is indicated that lactate is produced by astrocytes under the regulation of glutamatergic tone. OBJECTIVES: Using in vivo microdialysis technique, we measured extracellular lactate concentrations in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) of rats. To investigate the role of the glutamate transporter in the modulation of footshock stress-induced energy demands in both brain regions, we attempted to determine whether the footshock stress-induced changes of extracellular lactate concentrations are attenuated by local perfusion of the glutamate uptake inhibitor dihydrokainate (DHK). RESULTS: Perfusion of 1.0 mM DHK produced an increase in basal extracellular lactate levels in the mPFC and BLA, whereas 0.1 mM DHK did not affect lactate concentrations in either region. DHK also attenuated stress-induced increment of extracellular lactate concentrations in the mPFC, and completely prevented it in the BLA. CONCLUSIONS: These results suggest that glutamate transporters regulate lactate availability in astrocytes and indicate that the rapid energy demand induced by glutamate contributes to local lactate production.

Dopamine D1 and D2 receptors regulate extracellular lactate and glucose concentrations in the nucleus accumbens.

Glucose and lactate have been shown to play a significant role in energy metabolism in the brain. In the present study, the relationship between extracellular glucose and lactate concentrations in the nucleus accumbens (NAC) was determined with in vivo microdialysis technique. We further evaluated the effect of dopamine (DA) receptor agonists on energy metabolism. Extracellular glucose levels were increased following inactivation of neurons by tetrodotoxin (TTX) perfusion, whereas neural activation by veratridine or K(+) perfusion decreased extracellular glucose concentrations. By contrast, lactate levels were increased by veratridine or K(+) perfusion, but were unaltered by TTX. Apomorphine (0.05 mg/kg), a mixed D1/D2 receptor agonist, did not alter the extracellular glucose and lactate concentrations, while a higher dose (0.5 mg/kg) increased them. Bromocriptine, a selective D2 receptor agonist, increased extracellular glucose, but not lactate concentrations. These results indicate that extracellular lactate levels may be a more suitable indicator of acute neural activation than glucose levels, and that simultaneous stimulation of D1 and D2 receptors enhances energy demands of DA neurons in the NAC.

Interleukin-13 stimulates the secretion of vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 by human oviductal epithelial cells.

OBJECTIVE: The aim of this study is to evaluate the effects of interleukin (IL)-13, a Th2 cytokine, on the production of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in human oviductal cells in vitro. STUDY DESIGN: Human oviductal epithelial cells (OECs) were isolated from five premenopausal patients. The secretion of VEGF(165) and sFlt-1 by cultured OECs in response to IL-13 was measured using an enzyme-linked immunosorbent assay. RESULTS: The secretion of VEGF(165) and sFlt-1 was detected in cultured OECs under untreated conditions. IL-13 enhanced the secretion of VEGF(165) and sFlt-1 by OECs in a dose-dependent manner. CONCLUSION: The present findings suggest that IL-13 is a regulatory factor of VEGF and sFlt-1 production in the human fallopian tubes. IL-13 in the local environment may stimulate oviductal vascular permeability by inducing the production of VEGF by oviductal cells. The modulation of VEGF secretion by IL-13 secreted by the peri-implantation embryo may contribute to the normal and pathological processes of human reproduction during the peri-implantation period.

Role of 5-HT(1A) receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala.

RATIONALE: Lactate has been shown to play a significant role in energy metabolism and reflect neural activity in the brain. OBJECTIVES: Using in vivo microdialysis technique, we measured extracellular lactate concentrations in the medial prefrontal cortex (mPFC) and the basolateral amygdaloid (BLA) nucleus of rats under electric foot shock stress. Moreover, to examine the role of serotonin (5-HT)(1A) receptors in brain energy metabolism in response to stressors, we attempted to determine whether the stress-induced changes of extracellular lactate levels in the mPFC and BLA are attenuated by tandospirone, a partial agonist at 5-HT(1A) receptors, or perospirone, a novel atypical antipsychotic with a 5-HT(1A) receptor partial agonist and 5-HT(2A)/dopamine-D(2) antagonist property. RESULTS: Foot shock stress led to an increase in extracellular lactate concentrations both in the mPFC and BLA. Tandospirone (2 mg/kg) attenuated the foot shock stress-induced increase of extracellular lactate concentrations in both of the brain regions, which was blocked by pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. On the other hand, perospirone (0.3 mg/kg) attenuated the increment of extracellular lactate concentrations in the mPFC and BLA, which was unaltered by pretreatment with WAY-100635. CONCLUSIONS: These results indicate that the foot shock stress-induced increase in lactate metabolism is partly regulated by 5-HT(1A) receptors both in cortical and limbic regions.