Valeriana officinalis root extract suppresses physical stress by electric shock and psychological stress by nociceptive stimulation-evoked responses by decreasing the ratio of monoamine neurotransmitters to their metabolites
© Jung et al.; licensee BioMed Central. 2014
Received: 11 April 2014
Accepted: 22 September 2014
Published: 11 December 2014
In this study, we investigate the effects of valerian root extracts (VE) on physical and psychological stress responses by utilizing a communication box.
Eight-week-old ICR mice received oral administration of VE (100 mg/kg/0.5 ml) or equal volume of distilled water in every day for 3 weeks prior to being subjected to physical or psychological stress for 3 days, which are induced by communication box developed for physical electric shock and psychological stress by nociceptive stimulation-evoked responses. The stress condition was assessed by forced swimming test and serum corticosterone levels. In addition, norepinephrine (NE), serotonin (5-HT), and their metabolites such as 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus and amygdala at 1 h after final stress condition, respectively.
Immobility time and corticosterone levels were significantly increased in both the physical and psychological stress groups compared to the control group. The administration of VE significantly reduced these parameters in both the physical and psychological stress groups. In addition, compared to the control group, physical and psychological stress groups showed significantly increased levels of MHPG-SO4 and 5-HIAA in the hippocampus and amygdala, respectively. The administration of VE significantly suppressed the increase of MHPG-SO4 and 5-HIAA in the two stress groups.
These results suggest that VE can suppress physical and psychological stress responses by modulating the changes in 5-HT and NE turnover in the hippocampus and amygdala.
KeywordsValeriana officinalis Physical stress Psychological stress Serotonin Norepinephrine Hippocampus Amygdala
Root extracts from Valeriana officinalis (VE) are popular herbal supplements and are widely used in the treatment of sleep disorders, anxiety, and epilepsy . VE shows protective effects against neurodegenerative diseases such as Parkinson’s disease [2, 3] and Alzheimer’s disease . VE tinctures have anti-oxidant effects, as indicated by the finding that the tinctures can inhibit the thiobarbituric acid-reactive substance production and deoxyribose degradation induced by various pro-oxidants in rat brain homogenates . In addition, VE can modulate anxiety and insomnia by interacting with different neurotransmitter systems [4–9].
It has been reported that amygdala and hippocampus is one of critical regions for controlling aversive stress directly . Monoamine neurotransmitters in the central nervous system, particularly serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), are essential in regulating cognition, mood, and emotion. Abnormal 5-HT and NE transmission plays a key role in the stress response and the mechanism of antidepressant action [11–13]. The relationship between 5-HT and NE is also important for regulation of the sympathetic adrenomedullary system under stress conditions [14–16]. Recently, psychological stress (PCS) has attracted significant attention because it has been shown to accelerate the risk of various diseases including diabetes and cardiovascular disease as well as aging [17–19]. In addition, NE and 5-HT levels decreases following chronic stress exposure in male rats, while these levels are increased in female rats following the same stress [20, 21]. Therefore, it is important to investigate the compounds affecting 5-HT and NE in males.
In previous studies, we have shown that VE decreases the plasma corticosterone levels in adult mice as well as d-galactose-induced aging mice . Others have reported that dichloromethane extracts from roots and rhizomes of V. wallichii significantly increases NE and dopamine levels without any significant alterations in serotonin levels . In this study, we investigate the effects of VE on stress-induced changes in monoamine metabolites following physical stress (PS) and PCS.
Six-week-old male ICR mice were purchased from OrientBio Inc. (Seongnam, South Korea). They were housed at 23°C with 60% humidity and a 12-h light/12-h dark cycle, with free access to food and tap water. Animal handling and care conformed with the guidelines established in order to comply with current international laws and policies (NIH Guide for the Care and Use of Laboratory Animals, NIH Publication No. 85-23, 1985, revised 1996), and were approved by the Institutional Animal Care and Use Committee (IACUC) of Seoul National University (SNU-120103-10). All of the experiments and procedures were designed to minimize the number of animals used and the suffering caused.
Administration of VE
PS and PCS exposure
PS and PCS models were developed in mice utilizing a communication box according to the method of Ogawa and Kuwabara . Briefly, a communication box was divided into room A and room B with a transparent acrylic board (16 cm × 16 cm × 64 cm). Room A included 8 small rooms with a plastic board-covered floor, and room B included 8 small rooms with a metal grid-exposed floor for electric insulation (Figure 1A). Mice in room B were given an electrical shock (0.3 mA for 10 s and rest for 2 min) for 60 min through the floor and exhibited nociceptive stimulation-evoked responses, such as jumping up, defecating, and crying. Mice in room A were only exposed to the responses of mice in room B to establish PCS model. Mice were subjected to PS and PCS for 60 min every morning (11:00-11:30) for 3 days before they were killed. At the end of the exposure, the mice were kept in the cages for 1 h before they were taken out.
Forced swimming test
At 1 h after last stress exposure, the mice were placed inside a 25 cm glass cylinder (with a 14 cm diameter) containing 20 cm of water that was maintained at 24 ± 2°C and were forced to swim for 6 min. Their immobility times were recorded using the video-based Ethovision System during the last 4 min of the 6 min test.
Corticosterone levels and tissue processing
Mice from all 5 groups (n = 7 in each group) were anesthetized with 100 mg/kg of Zoletil 50® (Virbac, Carros, France) at 2 h after FST test to measure the concentrations of corticosterone levels in serum and 5-HT, NE, and their respective metabolites (5-hydroxyindoleacetic acid [5-HIAA] and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate [MHPG-SO4]) in the hippocampus and amygdala. Blood samples were obtained from each animal by cardiac puncture via the 1 ml syringe before obtaining the hippocampus and dentate gyrus. The samples were allowed to clot and were then centrifuged for 30 min at 1,000 g to separate out the serum. Corticosterone was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (IBL, Hamburg, Germany) following the manufacturer’s instructions. The absorbance was read at 450 nm. Brain was removed from braincase and the hippocampus and amygdala were separated on ice, and the samples were frozen using liquid nitrogen.
Monoamines and their metabolites in hippocampus and amygdala
5-HT, NE, 5-HIAA, and MHPG-SO4 concentrations were assessed in the mixture of hippocampal and amygdala samples by high-performance liquid chromatography (HPLC) as described by Nadaoka et al. . The frozen tissues were fractured in 0.2 M perchloric acid containing 0.1 mM disodium ethylenediaminetetraacetic acid (EDTA) and isoproterenol as an internal standard. The homogenate was then centrifuged at 20,000 × g for 15 min. The supernatant was adjusted to pH 3.0 with 1 M sodium acetate and then passed through a 0.2-μm regenerated cellulose filter. An aliquot of this filter was injected onto a C18 reverse-phase column (250 mm × 4.6 mm, 5 μm; Agilent Technologies, Santa Clara, CA) in a HPLC system (Agilent 1100 series) equipped with an electrochemical detector. The mobile phase used with this aliquot (0.1 M acetate-citrate buffer with 17% methanol) allowed for the separation of the two major monoamines 5-HT and NE and their respective metabolites, 5-HIAA and MHPG-SO4. Sodium octyl sulfate (190 mg/L) was added as an ion-pairing agent, and EDTA (5 mg/L) was added as an antioxidant. Each peak area was normalized to isoproterenol concentration. The level of 5-HT, NE and their metabolites were detected using a Waters 474 scanning fluorescence detector (Waters, USA) with its adequate excitation and emission wavelengths. The HPLC system was connected to a computer to quantify all compounds by comparing the area under the peaks with the area of reference standards with specific HPLC software (Chromatography Station for Windows). The turnover ratio of 5-HIAA to 5-HT is considered an index of the activity of cells that cause release of 5-HT, re-uptake and metabolism to 5-HIAA.
The data represent the mean values for each experiment. To determine the effects of VE on PS and PCS, the differences between the means were statistically analyzed by using a one-way analysis of variance with Tukey’s post-hoc test.
Effects of VE on depressive-like behavior in the stressed mice
The immobility time of the PS-VE group was significantly decreased; it was 84.5% of that in the PS-V group. On the other hand, in the PCS-V group, immobility time was significantly increased to 125.6% of that in the control group. In the PCS-VE group, immobility time was significantly decreased compared to that in the PCS-V group (Figure 1B).
Effects of VE on corticosterone levels following PS or PCS
Effects of VE on NE and MHPG-SO4 levels and their ratio following PS or PCS
Effects of VE on 5-HT and 5-HIAA levels and their ratio following PS or PCS
There has been growing interest in PS and PCS, as they are important factors in many disorders, such as hypertension, gastric ulcers, affective disorders, and metabolic syndromes. In the present study, we designed the communication box to induce PS and PCS in mice because this device can induce both PS and PCS models simultaneously and aid in investigating the physical and physiological changes under psychological stress conditions [28, 29].
The forced swimming test (FST) is a well-known screening tool for depressed animals [30, 31]. Depression of active behavior happens in animals with exposure to highly stressful situations. In the present study, we observed that immobility time of PS-V group was moderately increased compared to that of the control group. In this study, we observed the immobility time was more prominently increased in the PCS-V group compared to that in the PS-V group. It was reported that the immobility time in the FST was increased by acute restraint stress in rat . In addition, acute stress induced the immobility time by 121% of control group in mice . Similar to these studies, we observed that immobility time in the FST was decreased in both PS and PCS groups compared to that in the control group. In addition, the immobility time was significantly decreased in both VE-treated groups compared to that in respective vehicle-treated groups. The present result suggests that VE may ameliorate PS or PCS induced depression.
It was reported that a remarkable increase of plasma corticosterone level during and after both PS and PCS stress exposures [29, 34]. Similar to these studies, we observed significant increase in plasma corticosterone after PS and PCS conditions in the present study. In addition, we found that VE administration significantly reduced increased plasma corticosterone levels after both PS and PCS. This result is supported by our and other previous studies showing that reduced the corticosterone levels in immobilization-induced stress mice and in chemically induced aging mice [22, 35]. The present result suggests that VE could reduce increased corticosterone level by PS and PCS.
Next, we investigated the effects of VE on levels of NE, 5-HT, and their respective metabolites in the homogenates of the hippocampus and amygdala, which are regions most vulnerable to stress and the major targets for corticosterone, NE, and 5-HT [36–38]. NE cells are located in the locus coeruleus and lateral tegmental areas, and their fibers are projected into most brain regions including the hippocampus and amygdala . MHPG-SO4 level has been considered to be more indicative of NE utilization in the brain [40–43]. In addition, it was reported that these amine-to-metabolite ratios are increased by restraint stress  and these ratios are very useful factor to determine the stress conditions in the central nervous system because antidepressants typically enhance monoaminergic neurotransmission by inhibiting neurotransmitter degradation or reuptake .
These results are supported by previous findings that PS causes a remarkable increase in NE turnover in various brain regions such as the cerebral cortex, midbrain, locus coeruleus, hypothalamus, amygdala, thalamus, and hippocampus, while PCS has been reported to cause an acute mild increase in NE turnover in the hypothalamus and amygdala . Agonists of the 5-HT1A receptor and selective 5-HT reuptake inhibitors are clinically useful for treating various anxiety disorders [47, 48]. 5-HT cells are mainly located in the midbrain raphe nuclei and their fibers are projected into the prefrontal cortex, amygdala, hippocampus, and nucleus accumbens [49, 50]. Abnormalities in the 5-HT system in the brain causes depression and anxiety disorders, largely demonstrated by the fact that most antidepressants increase extracellular 5-HT level.
The dissociation of 5-HT and 5-HIAA was supported by previous studies on stress response showing that increased brain levels of 5-HIAA without affecting 5-HT concentrations under stress condition [51–54]. The ratio of 5-HIAA/5-HT was also significantly increased in the PS-V and PCS-V groups compared to the control group. The administration of VE to the PS or PCS group decreased the ratio of 5-HIAA/5-HT prominently (but not significantly) or significantly, respectively. Therefore, the present results suggest that PS or PCS stress is more prominently affected on changes of 5-HIAA levels than 5-HT levels, and VE administration could be reduced the ratio of 5-HIAA/5-HT via controlling of 5-HIAA levels in the PS or PCS condition. In addition, in both VE-treated groups, 5-HT levels also did not change significantly similar to previous study that showed any significant alterations in 5-HT levels after administration of dichloromethane extract from the roots and rhizomes of V. wallichii.
PS is induced by foot-shock stress, and PCS is generated by an exposure to the emotional responses caused by animal exposed to PS. PS and PCS animals significantly increase immobility time in forced swimming test, corticosterone levels in serum and turnover of 5-HT and NE in hippocampal and amygdala homogenates. PS dominantly modulates NE turnover, while PCS has a greater influence on 5-HT turnover. VE administration significantly suppresses the PS and PCS response by reducing the immobility time in forced swimming test, plasma levels of corticosterone and turnover of 5-HT and NE. These results suggest that VE could be ameliorated PS or PCS stress induced depression via control of plasma levels of corticosterone and turnover of 5-HT and NE.
This Research was supported by High Value-added Food Technology Development Program, Ministry for Agriculture, Food and Rural Affairs, Republic of Korea (111118-032-HD110).
- Hadley S, Petry JJ: Valerian. Am Fam Phys. 2003, 67: 1755-1758.Google Scholar
- De Oliveria DM, Barreto G, De Andrade DV, Saraceno E, Aon-Bertolino L, Capani F, Dos Santos El Bachá R, Giraldez LD: Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease. Neurochem Res. 2009, 34: 215-220. 10.1007/s11064-008-9749-y.View ArticlePubMedGoogle Scholar
- Pereira RP, Fachinetto R, de Souza Prestes A, Wagner C, Sudati JH, Boligon AA, Athayde ML, Morsch VM, Rocha JB: Valeriana officinalis ameliorates vacuous chewing movements induced by reserpine in rats. J Neural Transm. 2011, 118: 1547-1557. 10.1007/s00702-011-0640-7.View ArticlePubMedGoogle Scholar
- Malva JO, Santos S, Macedo T: Neuroprotective properties of Valeriana officinalis extracts. Neurotox Res. 2004, 6: 131-140. 10.1007/BF03033215.View ArticlePubMedGoogle Scholar
- Sudati JH, Fachinetto R, Pereira RP, Boligon AA, Athayde ML, Soares FA, de Vargas Barbosa NB, Rocha JB: In vitro antioxidant activity of Valeriana officinalis against different neurotoxic agents. Neurochem Res. 2009, 34: 1372-1379. 10.1007/s11064-009-9917-8.View ArticlePubMedGoogle Scholar
- Ortiz JG, Rassi N, Maldonado PM, González-Cabrera S, Ramos I: Commercial valerian interactions with [3H]flunitrazepam and [3H]MK-801 binding to rat synaptic membranes. Phytother Res. 2006, 20: 794-798. 10.1002/ptr.1960.View ArticlePubMedGoogle Scholar
- Sichardt K, Vissiennon Z, Koetter U, Brattström A, Nieber K: Modulation of postsynaptic potentials in rat cortical neurons by valerian extracts macerated with different alcohols: involvement of adenosine A1- and GABAA-receptors. Phytother Res. 2007, 21: 932-937. 10.1002/ptr.2197.View ArticlePubMedGoogle Scholar
- Del Valle-Mojica LM, Cordero-Hernández JM, González-Medina G, Ramos-Vélez I, Berríos-Cartagena N, Torres-Hernández BA, Ortíz JG: Aqueous and ethanolic Valeriana officinalis extracts change the binding of ligands to glutamate receptors. Evid Based Complement Alternat Med. 2011, 2011: 891819-PubMedGoogle Scholar
- Del Valle-Mojica LM, Ayala-Marín YM, Ortiz-Sanchez CM, Torres-Hernández BA, Abdalla-Mukhaimer S, Ortiz JG: Selective interactions of Valeriana officinalis extracts and valerenic acid with [H]glutamate binding to rat synaptic membranes. Evid Based Complement Alternat Med. 2011, 2011: 403591-PubMedPubMed CentralGoogle Scholar
- Maren S, Quirk GJ: Neuronal signalling of fear memory. Nat Rev Neurosci. 2004, 5: 844-852. 10.1038/nrn1535.View ArticlePubMedGoogle Scholar
- Ressler KJ, Nemeroff CB: Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 2000, 12 (Suppl 1): 2-19.View ArticlePubMedGoogle Scholar
- Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM: Neurobiology of depression. Neuron. 2002, 34: 13-25. 10.1016/S0896-6273(02)00653-0.View ArticlePubMedGoogle Scholar
- Wong ML, Licinio J: From monoamines to genomic targets: a paradigm shift for drug discovery in depression. Nat Rev Drug Discov. 2004, 3: 136-151. 10.1038/nrd1303.View ArticlePubMedGoogle Scholar
- Khan S, Michaud D, Moody TW, Anisman H, Merali Z: Effects of acute restraint stress on endogenous adrenomedullin levels. Neuroreport. 1999, 10: 2829-2833. 10.1097/00001756-199909090-00024.View ArticlePubMedGoogle Scholar
- Tanaka M, Yoshida M, Emoto H, Ishii H: Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. Eur J Pharmacol. 2000, 405: 397-406. 10.1016/S0014-2999(00)00569-0.View ArticlePubMedGoogle Scholar
- Chen WW, He RR, Li YF, Li SB, Tsoi B, Kurihara H: Pharmacological studies on the anxiolytic effect of standardized Schisandra lignans extract on restraint-stressed mice. Phytomedicine. 2011, 18: 1144-1147. 10.1016/j.phymed.2011.06.004.View ArticlePubMedGoogle Scholar
- Wales JK: Does psychological stress cause diabetes?. Diabet Med. 1995, 12: 109-112. 10.1111/j.1464-5491.1995.tb00439.x.View ArticlePubMedGoogle Scholar
- Blumenthal JA, Babyak MA, Doraiswamy PM, Watkins L, Hoffman BM, Barbour KA, Herman S, Craighead WE, Brosse AL, Waugh R, Hinderliter A, Sherwood A: Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007, 69: 587-596. 10.1097/PSY.0b013e318148c19a.View ArticlePubMedPubMed CentralGoogle Scholar
- Epel ES: Psychological and metabolic stress: a recipe for accelerated cellular aging?. Hormones (Athens). 2009, 8: 7-22. 10.14310/horm.2002.1217.View ArticleGoogle Scholar
- Bowman RE, Beck KD, Luine VN: Chronic stress effects on memory: sex differences in performance and monoaminergic activity. Horm Behav. 2003, 43: 48-59. 10.1016/S0018-506X(02)00022-3.View ArticlePubMedGoogle Scholar
- Luine VN: Sex differences in chronic stress effects on memory in rats. Stress. 2002, 5: 205-216. 10.1080/1025389021000010549.View ArticlePubMedGoogle Scholar
- Nam SM, Choi JH, Yoo DY, Kim W, Jung HY, Kim JW, Kang SY, Park J, Kim DW, Kim WJ, Yoon YS, Hwang IK: Valeriana officinalis extract and its main component, valerenic acid, ameliorate D-galactose-induced reductions in memory, cell proliferation, and neuroblast differentiation by reducing corticosterone levels and lipid peroxidation. Exp Gerontol. 2013, 48: 1369-1377. 10.1016/j.exger.2013.09.002.View ArticlePubMedGoogle Scholar
- Sah SP, Mathela CS, Chopra K: Antidepressant effect of Valerianan wallichii patchouli alcohol chemotype in mice: behavioural and biochemical evidence. J Ethnopharmacol. 2011, 135: 197-200. 10.1016/j.jep.2011.02.018.View ArticlePubMedGoogle Scholar
- Tang JY, Zeng YS, Chen QG, Qin YJ, Chen SJ, Zhong ZQ: Effects of Valerian on the level of 5-hydroxytryptamine, cell proliferation and neurons in cerebral hippocampus of rats with depression induced by chronic mild stress. Zhong Xi Yi Jie He Xue Bao. 2008, 6: 283-288. 10.3736/jcim20080313.View ArticlePubMedGoogle Scholar
- Ogawa M, Kuwabara H: Psychophysiology of emotion-communication of emotion. Shinshin-Igaku. 1966, 6: 352-357.Google Scholar
- Nadaoka I, Yasue M, Sami M, Kitagawa Y: Oral administration of Cimicifuga racemosa extract affects immobilization stress-induced changes in murine cerebral monoamine metabolism. Biomed Res. 2012, 33: 133-137. 10.2220/biomedres.33.133.View ArticlePubMedGoogle Scholar
- Rowland NE, Dunn AJ: Effect of dexfenfluramine on metabolic and neurochemical measures in restraint-stressed ob/ob mice. Physiol Behav. 1995, 58: 749-754. 10.1016/0031-9384(95)00105-R.View ArticlePubMedGoogle Scholar
- Endo Y, Shiraki K: Behavior and body temperature in rats following chronic foot shock or psychological stress exposure. Physiol Behav. 2000, 71: 263-268. 10.1016/S0031-9384(00)00339-5.View ArticlePubMedGoogle Scholar
- Endo Y, Yamauchi K, Fueta Y, Irie M: Changes of body temperature and plasma corticosterone level in rats during psychological stress induced by the communication box. Med Sci Monit. 2001, 7: 1161-1165.PubMedGoogle Scholar
- Porsolt R, Bertin A, Jalfre M: Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977, 229: 327-336.PubMedGoogle Scholar
- Petit-Demouliere B, Chenu F, Bourin M: Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl). 2005, 177: 245-255. 10.1007/s00213-004-2048-7.View ArticleGoogle Scholar
- Cancela L, Rossi S, Molina V: Effect of different restraint schedules on the immobility in the forced swim test: modulation by an opiate mechanism. Brain Res Bull. 1991, 26: 671-675. 10.1016/0361-9230(91)90159-H.View ArticlePubMedGoogle Scholar
- Poleszak E, Wlaz P, Kêdzierska E, Nieoczym D, Wyska E, Szymura-Oleksiak J, Fidecka S, Radziwon-Zaleska M, Nowak G: Immobility stress induces depression-like behavior in the forced swim test in mice: effect of magnesium and imipramine. Pharmacol Rep. 2006, 58: 746-PubMedGoogle Scholar
- Ishikawa M, Hara C, Ohdo S, Ogawa N: Plasma corticosterone response of rats with sociopsychological stress in the communication box. Physiol Behav. 1992, 52: 475-480. 10.1016/0031-9384(92)90333-W.View ArticlePubMedGoogle Scholar
- Hosoi J, Tanida M, Tsuchiya T: Mitigation of stress-induced suppression of contact hypersensitivity by odorant inhalation. Br J Dermatol. 2001, 145: 716-719. 10.1046/j.1365-2133.2001.04409.x.View ArticlePubMedGoogle Scholar
- Henke PG, Ray A, Sullivan RM: The amygdala: emotions and gut functions. Dig Dis Sci. 1991, 36: 1633-1643. 10.1007/BF01296409.View ArticlePubMedGoogle Scholar
- Conrad CD: Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis. Rev Neurosci. 2008, 19: 395-411.View ArticlePubMedPubMed CentralGoogle Scholar
- Joëls M, Krugers H, Karst H: Stress-induced changes in hippocampal function. Prog Brain Res. 2008, 167: 3-15.View ArticlePubMedGoogle Scholar
- Moore RY, Bloom FE: Central catecholamine neuron systems: anatomy and physiology of the norepinephrine and epinephrine systems. Annu Rev Neurosci. 1979, 2: 113-168. 10.1146/annurev.ne.02.030179.000553.View ArticlePubMedGoogle Scholar
- Stone EA: Stress and catecholamines. Catecholamines and Behavior. Edited by: Friedhoff AJ. 1975, New York: Plenum, 31-72.View ArticleGoogle Scholar
- Elsworth JD, Roth RH, Redmond DE: Relative importance of 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol as norepinephrine metabolites in rat, monkey, and humans. J Neurochem. 1983, 41: 786-793. 10.1111/j.1471-4159.1983.tb04809.x.View ArticlePubMedGoogle Scholar
- Kohno Y, Tanaka M, Nakagawa R, Toshima N, Nagasaki N: Regional distribution and production rate of 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MHPG-SO4) in rat brain. J Neurochem. 1981, 36: 286-289. 10.1111/j.1471-4159.1981.tb02405.x.View ArticlePubMedGoogle Scholar
- Meek JL, Neff NH: The rate of formation of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in brain as an estimate of the rate of formation of norepinephrine. J Pharmacol Exp Ther. 1973, 184: 570-575.PubMedGoogle Scholar
- Sudha S, Pradhan N: Stress-induced changes in regional monoamine metabolism and behavior in rats. Physiol Behav. 1995, 57: 1061-1066. 10.1016/0031-9384(94)00369-G.View ArticlePubMedGoogle Scholar
- Baudry A, Mouillet-Richard S, Launay JM, Kellermann O: New views on antidepressant action. Curr Opin Neurobiol. 2011, 21: 858-865. 10.1016/j.conb.2011.03.005.View ArticlePubMedGoogle Scholar
- Tanaka M, Tsuda A, Yokoo H, Yoshida M, Ida Y, Nishimura H: Involvement of the brain noradrenaline system in emotional changes caused by stress in rats. Ann N Y Acad Sci. 1990, 597: 159-174. 10.1111/j.1749-6632.1990.tb16165.x.View ArticlePubMedGoogle Scholar
- Coplan JD, Gorman JM, Klein DF: Serotonin related functions in panic-anxiety: a critical overview. Neuropsychopharmacology. 1992, 6: 189-200.PubMedGoogle Scholar
- De Vry J: 5-HT1A receptor agonists: recent developments and controversial issues. Psychopharmacology (Berl). 1995, 121: 1-26. 10.1007/BF02245588.View ArticleGoogle Scholar
- Holmes A: Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci Biobehav Rev. 2008, 32: 1293-1314. 10.1016/j.neubiorev.2008.03.006.View ArticlePubMedPubMed CentralGoogle Scholar
- Steinbusch HW: Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience. 1981, 6: 557-618. 10.1016/0306-4522(81)90146-9.View ArticlePubMedGoogle Scholar
- Li JM, Kong LD, Wang YM, Cheng CH, Zhang WY, Tan WZ: Behavioral and biochemical studies on chronic mild stress models in rats treated with a Chinese traditional prescription Banxia-houpu decoction. Life Sci. 2003, 74: 55-73. 10.1016/j.lfs.2003.06.030.View ArticlePubMedGoogle Scholar
- Tõnissaar M, Herm L, Eller M, Kõiv K, Rinken A, Harro J: Rats with high or low sociability are differently affected by chronic variable stress. Neuroscience. 2008, 152: 867-876. 10.1016/j.neuroscience.2008.01.028.View ArticlePubMedGoogle Scholar
- Adell A, Garcia-Marquez C, Armario A, Gelpi E: Chronic stress increases serotonin and noradrenaline in rat brain and sensitizes their responses to a further acute stress. J Neurochem. 1988, 50: 1678-1681. 10.1111/j.1471-4159.1988.tb02462.x.View ArticlePubMedGoogle Scholar
- Mitchell SN, Thomas PJ: Effect of restraint stress and anxiolytics on 5-HT turnover in rat brain. Pharmacology. 1988, 37: 105-113. 10.1159/000138453.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/14/476/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.