Temporomandibular inflammation mobilizes parvalbumin and FosB/deltaFosB neurons of amygdala and dorsal raphe

Pathophysiological mechanisms involved in orofacial pain and their relationship with emotional disorders have emerged as an important research area for multidisciplinary studies. In particular, temporomandibular disorders (TMD) have been evaluated clinically from both physiological and psychological perspectives. We hypothesized that an altered neuronal activity occurs in the amygdala and the dorsal raphe nucleus (DR), encephalic regions involved in the modulation of painful and emotional information. Adult male Wistar rats were used in an experimental complete Freund's adjuvant (CFA)-induced temporomandibular joint (TMJ) inflammation model. CFA was applied for 1 or 10 days, and the animals were euthanized for brain samples dissection for FosB/ΔFosB and parvalbumin (PV) immunostaining. Our results were consistent in showing that the amygdala and DR were activated in the persistent inflammatory phase (10 days) and that the expression of PV+ interneurons in the amygdala was decreased. In contrast, in the DR, the expression of PV+ interneurons was increased in persistent states of CFA-induced TMJ inflammation. Moreover, at 10 days of inflammation, there was an increased co-localization of PV+ and FosB/ΔFosB+ neurons in the basolateral and central nucleus of the amygdala. Different nuclei of the amygdala, as well as portions of the DR, were activated in the persistent phase (10 days) of TMJ inflammation. In conclusion, altered activity of the amygdala and DR was detected during persistent inflammatory nociception in the temporomandibular joint. These regions may be essential for both sensory and affective dimensions of orofacial pain.

Effects of Temporary Inactivation and Electrical Stimulation of the Dorsal Raphe Nucleus on Morphine-induced Conditioned Place Preference

Background: The dorsal raphe nucleus (DRN) influences a wide range of behavioral and reward function. In this study, we evaluated electrical stimulation and inactivation of DRN on morphine conditioned place preference (CPP). Methods: The rats were anesthetised (n = 7 for each group) and the electrode and cannula were implanted into the DRN by stereotaxic instrument. Electrical stimulation (100μA) and reversible inactivation by lidocaine were induced into DRN and then morphine-induced CPP was investigated. Results: The stimulation of DRN in combination with effective dose of morphine showed a significant decrease only on expression phases 20s (SD 33.7) when compared with morphine group 119.85s (SD 23.7) (One way ANOVA, Tukey’s; P = 0.036). Also, this stimulation in combination with ineffective dose of morphine showed a significant increase only on acquisition phases 67.5s (SD 41.2) of CPP compared with morphine group -46s (SD 18.51) (P = 0.034). Also, there were not significant differences in inactivation of DRN by lidocaine on different phase of CPP (P = 0.091). Conclusion: It is possible that electrical stimulation of the DRN with changes in concentration of serotonin or involving other transmitters such as glutamate and gamma amino butyric acid (GABA) would be involved to these changes of CPP.

Fos expression in the prefrontal cortex and mesencephalic dorsal raphe nucleus in lactating rats after social instigation

Females are often less aggressive than males, but they exhibit high levels of agonistic behavior against an intruder in the area of ​​the nest during lactation. This behavior is referred to as maternal aggression. In rats, maternal aggressive behavior occurs more often from postpartum day 3 (PPD 3) to PPD 12. Social instigation is an experimental protocol used to increase the levels of aggression that are typical of the species. In the present study we used social instigation to analyze the expression of a marker of neuronal activity, c-fos. Lactating rats on PPD 5, in the presence of their pups, were divided into four groups: (1) no social instigation and no aggressive behavior, (2) social instigation and no aggressive behavior, (3) no social instigation and aggressive behavior, and (4) social instigation and aggressive behavior. Sixty minutes after the aggression test we used immunohistochemistry to detect Fos in two brain regions, the ventral-orbital region of the prefrontal cortex (VO PFC) and dorsal raphe nucleus (DRN). Our results showed that rats with aggressive behavior that were provoked exhibited an increase in Fos expression in the VO PFC compared with the control group (i.e., no social instigation and no aggressive behavior). No change in Fos expression was found in the DRN. These results complement previous findings with microinjection of serotonin 5-hydroxytryptamine-1B receptor agonists into the same region, demonstrating that the VO PFC is an important region in the modulation of maternal aggressive behavior.

Efeito do lítio sobre a hiperatividade locomotora induzida pela lesão eletrolítica da região do núcleo mediano da rafe em ratos / Effect of lithium treatment on the locomotor hyperactivity induced by the lesion of the region of the median raphe nucleus in rats

A lesão do núcleo mediano da rafe (NMR) produz sintomas que sugerem validade de face ao episódio maníaco. Esta pesquisa avaliou o efeito do lítio sobre a hiperatividade locomotora induzida por esta lesão. Vinte e um ratos Wistar machos foram submetidos à lesão eletrolítica da região do NMR (LR) e 17 foram submetidos à lesão fictícia (LF). Após recuperação, a atividade locomotora foi avaliada na caixa de atividade (Med Associates/ENV-515). Parte dos animais destes grupos recebeu tratamentos com lítio (47,5 mg/kg/2x dia i.p.) por 10 dias, enquanto o restante foi tratado com salina no mesmo esquema. A reavaliação ao final dos tratamentos demonstrou que o lítio reduziu significantemente a atividade locomotora em relação à avaliação inicial no grupo LR (ANOVA/Bonferroni p < 0,05), tornando-a equivalente aos baixos níveis dos grupos LF. Estes dados sustentam a hipótese de que as manifestações induzidas pela lesão do NMR podem constituir um modelo animal de mania.

The lesion of the Median Raphe Nucleus (MRN) produces symptoms that suggest face validity for manic episodes. This research evaluated the effect of lithium treatment on the locomotor hyperactivity induced by this lesion. Twenty-one Wistar male rats were submitted to the lesion of the region of the MRN (LR) and 17 were sham lesioned (LF). After recovery, the locomotor activity was evaluated in an activity chamber (Med Associates/ENV-515). A subgroup received lithium (47.5 mg/kg/twice a day i.p.) for 10 days, while the other animals received saline in the same schedule. The reevaluation at the end of the treatments showed that only lithium significantly reduced the activity of LR group compared to baseline levels (ANOVA/Bonferroni p < 0.05), making it equivalent to low levels of LF groups. These data support the hypothesis that the behavioral manifestations induced by the lesion of the MRN may constitute an animal model of mania.

5-HT1A autoreceptor modulation of locomotor activity induced by nitric oxide in the rat dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is the origin of ascending serotonergic projections and is considered to be an important component of the brain circuit that mediates anxiety- and depression-related behaviors. A large fraction of DRN serotonin-positive neurons contain nitric oxide (NO). Disruption of NO-mediated neurotransmission in the DRN by NO synthase inhibitors produces anxiolytic- and antidepressant-like effects in rats and also induces nonspecific interference with locomotor activity. We investigated the involvement of the 5-HT1A autoreceptor in the locomotor effects induced by NO in the DRN of male Wistar rats (280-310 g, N = 9-10 per group). The NO donor 3-morpholinosylnomine hydrochloride (SIN-1, 150, and 300 nmol) and the NO scavenger S-3-carboxy-4-hydroxyphenylglycine (carboxy-PTIO, 0.1-3.0 nmol) were injected into the DRN of rats immediately before they were exposed to the open field for 10 min. To evaluate the involvement of the 5-HT1A receptor and the N-methyl-D-aspartate (NMDA) glutamate receptor in the locomotor effects of NO, animals were pretreated with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 8 nmol), the 5-HT1A receptor antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635, 0.37 nmol), and the NMDA receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (AP7, 1 nmol), followed by microinjection of SIN-1 into the DRN. SIN-1 increased the distance traveled (mean ± SEM) in the open-field test (4431 ± 306.1 cm; F7,63 = 2.44, P = 0.028) and this effect was blocked by previous 8-OH-DPAT (2885 ± 490.4 cm) or AP7 (3335 ± 283.5 cm) administration (P < 0.05, Duncan test). These results indicate that 5-HT1A receptor activation and/or facilitation of glutamate neurotransmission can modulate the locomotor effects induced by NO in the DRN.

Changes in firing rate and firing pattern of midbrain dopaminergic neurons after lesioning of the dorsal raphe nucleus by 5,7-drhydroxytryptamine in adult rats / 西安交通大学学报·英文版

Objective: To study the effect of serotonergic efferent projection of the dorsal raphe nucleus (DRN) on the activity of substantia nigra pars compacta (SNc) and ventral tegmenta area (VTA) dopaminergic neurons after lesioning of the DRN by the neurotoxin 5,7-drhydroxytryptamine (5,7-DHT) in rat. Methods: The changes in the firing rate and firing pattern of SNc and VTA dopaminergic neurons were observed with extracellular recording in control and the lesioned rats. Results: The results showed that the mean firing rates of the fast-firing dopaminergic neurons of the SNc in control and the lesioned rats were (5.34±0.13) Hz (n=23) and (7.13±0.49) Hz (n=37), respectively. The mean firing rate of the fast-firing dopaminergic neurons of the SNc in the lesioned rats was significantly increased when compared to that of control rats (P<0.01), while the mean firing rate of the slow-firing dopaminergic neurons of the SNc did not change. The mean firing rates of dopaminergic neurons of the VTA in control and the lesioned rats were (5.27±0.38) Hz (n=35) and (3.6±0.2) Hz (n=52), respectively. Lesioning of the DRN induced a significant decrease in the mean firing rate of dopaminergic neurons of the VTA. The firing pattern of SNc and VTA dopaminergic neurons changed towards a more bursting or irrgular firing after the lesioning. Conclusion: These data suggest that the serotonergic efferent projections of the DRN significantly affect the activity of SNc and VTA dopaminergic neurons.

Changes in firing rate and firing pattern of midbrain dopaminergic neurons after lesioning of the dorsal raphe nucleus by 5,7-drhydroxytryptamine in adult rats / 药物分析学报

Objective To study the effect of serotonergic efferent projection of the dorsal rophe nucleus (DRN) on the activity of substantia nigro pars compacta (SNc) and ventral tegmenta area (VTA) dopaminergic neurons after lesioning of the DRN by the neurotoxin 5,7-drhydroxytryptamine (5,7-DHT) in rot. Methods The changes in the firing rote and firing pattern of SNc and VTA dopaminergic neurons were observed with extrocellular recording in control and the lesioned rats. Results The results showed that the mean firing rotes of the fast-firing dopaminergic neurons of the SNc in control and the lesioned rots were (5.34±0. 13 ) Hz (n = 23 ) and ( 7.13±0. 49 ) Hz (n=37), respectively. The mean firing rote of the fast-firing dopaminergic neurons of the SNc in the lesioned rats was significantly increased when compared to that of control rots (P<0.01), while the mean firing rote of the slow-firing dopaminergic neurons of the SNc did not change. The mean firing rotes of dopaminergic neurons of the VTA in control and the lesioned rots were (5.27±0. 38)Hz (n=35) and (3.6±0.2)Hz (n=52), respectively. Lesioning of the DRN induced a significant decrease in the mean firing rote of dopaminergic neurons of the VTA. The firing pattern of SNc and VTA dopaminergic neurons changed towards a more bursting or irrgular firing after the lesioning. Conlusion These data suggest that the serotonergic efferent projections of the DRN significantly affect the activity of SNe and VTA dopaminergic neurons.

Role of the serotoninergic system in the sodium appetite control

The present article reviews the role of the serotoninergic system in the regulation of the sodium appetite. Data from the peripheral and icv administration of serotoninergic (5-HTergic) agents showed the participation of 5-HT2/3 receptors in the modulation of sodium appetite. These observations were extended with the studies carried out after brain serotonin depletion, lesions of DRN and during blockade of 5-HT2A/2C receptors in lateral parabrachial nucleus (LPBN). Brain serotonin depletion and lesions of DRN increased the sodium appetite response, in basal conditions, after sodium depletion and hypovolemia or after beta-adrenergic stimulation as well. These observations raised the hypothesis that the suppression of ascending pathways from the DRN, possibly, 5-HTergic fibers, modifies the angiotensinergic or sodium sensing mechanisms of the subfornical organ involved in the control of the sodium appetite. 5-HTergic blockade in LPBN induced to similar results, particularly those regarded to the natriorexigenic response evoked by volume depletion or increase of the hypertonic saline ingestion induced by brain angiotensinergic stimulation. In conclusion, many evidences lead to acceptation of an integrated participation resulting of an interaction, between DRN and LPBN, for the sodium appetite control.

Este artigo revisa o papel do sistema serotoninérgico no controle do apetite ao sódio. Dados derivados da administração periférica e icv de agentes serotoninérgicos demonstraram a participação de receptores 5-HT2/3 na modulação do apetite ao sódio. Estas observações foram estendidas com os estudos realizados após a depleção cerebral de serotonina, lesões do NDR e durante o bloqueio 5-HT2A/2C no núcleo parabraquial lateral (NPBL). A depleção cerebral de serotonina e as lesões do NDR aumentaram o apetite ao sódio, em condições basais, após depleção de sódio, durante a hipovolemia ou após a estimulação beta-adrenérgica. Estas evidências suscitaram a hipótese de que a supressão de vias ascendentes do NDR, possivelmente 5-HT, alteram os mecanismos angiotensinérgicos e a atividade dos sensores de sódio do órgão subfornicial envolvidos no controle do apetite ao sódio. O bloqueio serotoninérgico no NPBL induziu a resultados similares, particularmente aqueles relacionados com a resposta natriorexigênica provocada pela depleção de volume ou o aumento da ingestão de salina hipertônica induzida pela estimulação angiotensinérgica cerebral. Em resumo, as evidências convergem para a admissão de uma participação integrada resultante da interação recíproca entre NDR e NPBL objetivando controlar o apetite ao sódio.

Effect of Exogenous Thyroxine on the Postnatal Development of Serotonin-containing Neuron in Fetal Alcohol Effects in the Rat Raphe Nuclei / 체질인류학회지

Serotonin (5-hydroxytryptamine, 5-HT) has been concerned in the pathophysiology of various neuropsychiatric disorders. It is known to modulate emotion, cognition, endocrine activity, motor function, and pain. In the present study, the effects of exogenous thyroxine (T4) on the postnatal development of serotonin-containing neuron in the rat raphe nuclei with fetal alcohol effects were investigated using immunohistochemistry. These experimental animals were divided into three groups : the alcohol-fed group received 35 calories liquid ethanol diet; the control pair-fed group was fed a liquid diet in dextrin replaced alcohol isocalorically; alcohol+T4 group received alcohol diet and exogenous thyroxine subcutaneously. After the pups were born, the pups of each were fostered by surragate mother. An average of four pups, one from each litter, were killed at days 0, 7, 14, 21, and 28 for each of the above three groups. As a result, in alcohol group, serotonin-immunoreactivity was weakly stained at all postnatal ages compared to control pair-fed and alcohol+T4 group. The intensity of serotonin immunoreactivity was more prominent in alcohlol+T4 group than in control pair-fed group at P0. Mature patterns of serotonin-containing neurons were observed in control pair-fed and alcohol+T4 group at P7. A similar developmental pattern of serotonin-containing neuron was observed on and after P7 in control pair-fed and alcohol+T4 group. These results suggest that the increase of serotonin synthesis during early postnatal life caused by maternal administration of exogenous thyroxine may ameliorate fetal alcohol effects, one of the ill effects as a result of the dysthyroid state following maternal alcohol abuse.

Elevated Serotonin-immunoreactive Neurons in the Raphe Nucleus of the Ataxic Mutant Mouse, Pogo / 대한해부학회지

This study was carried out to investigate the distribution of serotonin-immunoreactive neruons in the raphe nucleus of the ataxic pogo (pogo/pogo) mice derived from a Korean wild mice. Using by immunohistochemistry, we undertook to elucidate any correlation between the serotonin expression and behavior ataxia including abnormal hindlimb extension in the ataxic pogo mice. The present study has two important findings. First, serotonin immunoreactivity was increased in the raphe nucleus of the ataxic pogo mice. Second, serotonin immunoreactivity was different with the region of raphe nucleus. In the dorsal part of dorsal raphe nucleus (DRD), ventrolateral part of dorsal raphe nucleus (DRVL) and median raphe nucleus (MR), serotonin immunoreactivity was increased, whereas the ventral part of dorsal raphe nucleus (DRV) and interfascicular part of dorsal raphe nucleus (DRI) was similar with the control mice. Therefore, elevated expression of the serotonin in the raphe nucleus of ataxic pogo mice might be a source of behavior ataxia and may be related with the induction of the ataxic phenotype including abnormal hindlimb movements.

HYPOXIA INDUCED EXPRESSION OF FOS IN THE DISTAL CEREBROSPINAL FLUID CONTACTING NEURONS IN THE DORSAL RAPHE NUCLEUS OF THE RAT / 神经解剖学杂志

The effects of hypoxia on the expression of Fos was studied in the distal cerebrospinal fluid contacting neurons (CSF-CNs) in the dorsal raphe nucleus (DR) of the rat. The hypoxic models mimic 8000 m high level were established in a high-altitude decompression chamber. Injecting the tracer of CB ( chorela toxin B subunit) into the rat's lateral ventricles, we investigated the distribution of the distal CSF-CNs in the DR. The single and double immunohistochemistry staining with antibodies to Fos and CB were used to observe the expression of Fos in the distal CSF-CNs in the DR. The results showed that a large number of CB-like immunoreactive (-LI) neurons (31.16 ±3.36/per section) were located in the DR. In hypoxic experimental rats, the number of Fos-LI neurons was increased sharply (40.28 ±2.17/per section, P ＜0.05 compared to control rats), and a few CB/Fos-LI neurons (2.00 ±0.39/per section) could be observed in the DR. In control rats, several Fos-LI neurons (5.55 ±0.81/per section) and no CB/Fos-LI neuron could be observed in the DR. These results suggest that some of the distal CSF-CNs in the DR may play roles in transmitting information between brain and cerebrospinal fluid and modulating the function of brain following hypoxic stimulation.

The Effect of Melatonin Injection into Rat Brain Stem with Chronic Stress on Serotonergic Immunoreactivity / 체질인류학회지

These experiments were performed to investigate the effect of saline, melatonin, stress, stressed-melatonin on serotonin immunoreactivity in rat brain stem. The animals were injected with melatonin (1 mg/kg, i.p.) after electric shocks for 15days. The results were as follows; 1. Serotonin immunoreactive neurons in brain stem (the number of staining neuron & the stain intensity in dorsal raphe nucleus of midbrain, the stain intensity in nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla oblongata) were decreased in melatonin treated group compared with all the other groups. 2. Serotonin immunoreactive neurons in brain stem (the number of staining neuron & the stain intensity in dorsal raphe nucleus of midbrain, the stain intensity in nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla oblongata) were significantly increased in stressed group compared with all the other groups. 3. Serotonin immunoreactive neurons in brain stem(the number of staining neuron & the stain intensity in dorsal raphe nucleus of midbrain, the stain intensity in nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla oblongata) were significantly decreased in stressed-melatonin treated group compared with only stressed group but were significantly increased compared with melatonin treated group. These experiments indicate that serotonin immunoreactive neurons in dorsal raphe nucleus of midbrain were increased, due to the activation of stress, and decreased when the activating of stress is suppressed through melatonin treatment.

The Effect of Photoperiod and Melatonin Injection on Serotonergic Immunoreactivity in Rat Brain Stem / 대한해부학회지

These experiments were performed to investigate the effect of photoperiod and melatonin on serotonergic immunoreactivity in rat brain stem. The animals were injected with melatonin (1 mg/kg, i.p.) after light and dark treatment. The results by immunohistochemical method were as follows; 1. Immunohistochemical serotonin intensity in brain stem (dorsal raphe nucleus of midbrain, nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla) appeard weakly in medium in control group compared with light and dark treated group. It suggest that enhanced effect in single injection (light or dark) was canceled by complex mechanism when two factors (light and dark) bring about together. 2. Serotonin immunoreactive neurons in brain stem (dorsal raphe nucleus of midbrain, nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla) were significantly increased in light and dark treated group compared with control group. These results show that serotonin pathways are more important in mediating the effects of retinally perceived light in the rat. 3. Serotonin immunoreactive neurons in brain stem (dorsal raphe nucleus of midbrain, nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla) were incresesed in melatonin treated group compared with melatonin non-treated group in light and dark. These results indicated that melatonin injection during photo and dark period enhanced serotonergic neurons activity and then light control influenced the development of serotonergic systems in brain stem including dorsal raphe nucleus of midbrain, nucleus tractus solitarius and dorsal nucleus of vagus nerve in medulla.

The nNOS expression in rat distal CSF contacting neurons and its relationship with morphine withdrawal / 中国药理学通报

Aim To observe the neuron nitric oxide synthase(nNOS) expression in the distal cerebrospinal fluid contacting neurons(CSF-CNs) of rat brain parenchyma, and investigate the role of CSF-CNs in the development of morphine dependence and withdrawal.Methods Male adult Sprague-Dawley rats, weighed 260?20 g,were experimented with A 3 ?l volume of 30% cholera toxin subunit B with horseradish peroxidase(CB-HRP) was injected into one of the rats′lateral ventricles to trace and locate the distal CSF-CNs of rat brain parenchyma 48 hours before the animals were killed. All animals were perfused and the relative tissue of rats′brain was removed.Frozen serial coronal sections (40 ?m) were cut. Then TMB-ST reaction procedure was used to stain the CB-HRP positive neurons,followed by immunohistochemistry double-labeling of the nNOS with CB-HRP positive neurons. The withdrawal symptoms were observed and scored. The numbers of the CB-HRP, and CB-HRP/nNOS positive neurons on the same segmental brain sections were counted.Results The withdrawal symptoms of the withdrawal group were significant, scores of all signs were significantly higher than those of the dependence groups and control group(P

The Effect of Treatment with Tryptophan and/or Imipramine on the Serotonergic Immunoreactivity in Raphe Nucleus of Midbrain of the Rats / 대한해부학회지

These experiments were performed to investigate the effect of saline, tryptophan, tryptophan-imipramine and/or imipramine on serotonin immunoreactivity in raphe nucleus of midbrain of the rats (180~200 g, body weight). The animals were injected i.p. with tryptophan (15 mg/kg) and imipramine (15 mg/kg) for 20 days. The result by immunohistochemical methods were as follows; 1. Serotonin-immunoreactive neurons in the raphe of midbrain were significantly increased in tryptophan treated group compared to imipramine treated group. 2. Serotonin-immunoreactive neurons in the raphe of midbrain were decreased in imipramine treated group compared all the other group. 3. Serotonin-immunoreactive neurons in the raphe of midbrain were significantly decreased in tryptophanimipramine treated group compared to imipramine treated group. These experiments indicated that serotonin immunoreactive neurons in raphe of midbrain were increased due to the activation of tryptophan and decreased by suppresing activation of tryptophan through imipramine treatment.

The Effect of Treatment with Imipramine and/or Tryptophan after Chronic Stress on the Serotonergic Immunoreactivity in Rat Raphe Nucleus / 대한해부학회지

These experiments were performed to investigate the effect of saline, stress, imipramine, stress -imipramine and/or stress -tryptophan on serotonin immunoreactivity in raphe nucleus of the rats (200 ~220 g, body weight). The animals were injected i.p. with imipramine (15 mg/kg) and tryptophan (15 mg/kg) after electric shocks for 20 days. The result by immunohistochemical methods were as follows; 1. Serotonin -immunoreactive neurons in the raphe nucleus of midbrain were significantly increased in stress treated group compared to saline treated group. 2. Serotonin -immunoreactive neurons in the raphe nucleus of midbrain were decreased in imipramine treated group compared all the other group. 3. Serotonin -immunoreactive neurons in the raphe nucleus of midbrain were significantly decreased in stress -imipramine treated group compared to stress alone treated group but were significantly increased in stress -imipramine treated group compared to imipramine treated group. 4. Serotonin -immunoreactive neurons in the raphe nucleus of midbrain were significantly increased in stress -tryptophan treated group compared to stress alone and saline treated group. These experiments indicated that serotonin immunoreactive neurons in raphe nucleus of midbrain were increased due to the activation of stress and decreased by suppresing activation of stress through imipramine treatment.

The effect of treatment with tryptophan and/or reserpine on the serotonergic immunoreactivity in raphe nucleus of medulla oblongata and midbrain of the rats / 대한해부학회지

The present study was carried out to investigate the effect of treatment with tryptophan and/or reserpine on the raphe of medulla oblongata and mid brain of the rats (180~200 g body weight). the animal were injected i.p. with reserpine (5 mg/kg) for 3 days and tryptophan (15 mg/kg) for 20 days. The results by immunohistochemical methods were as follows: 1. Serotonin-immunoreactive neurons in the raphe of medulla oblongata and mid brain decrease in reserpine treated group compared to all the other group. 2. Serotonin-immunoreactive neurons in the raphe of medulla oblongata and mid brain were increased in tryptophan -reserpine treated group compared to the reserpine treated group but not the tryptophan treated group. 3. Serotonin-immunoreactive neurons in the raphe of medulla oblongata and mid brain were inceased in tryptophan treated group compared to all the other group. The experiments indicated that serotonin immunoreactive neurons in medulla oblongata and mid brain increased due to the activation of tryptophan and decreased by suppressing activation of tryptophan through reserpine.

Cytotoxic Effect of 6-OHDA on the Dopaminergic Neurons and Astrocytes in the Dorsal Raphe Nucleus of the Rat / 대한해부학회지

This study was designed to clarify the cytotoxic effects of 6-hydroxydopamine (6-OHDA) on the dopaminergic neurons and astrocytes in the dorsal raphe nucleus (DRN), and to investigate neurodegenerative changes by immuno-histochemistry. Adult male rats (Sprague-Dawley strain) weighing from 250 to 350 g were used as experimental animals. 6-OHDA (100 micrometer dissolved in 0.1% ascorbic acid) was injected into the lateral ventricle of the rat brain with the Hamilton syringe. The control rats were treated with the similar volume of 0.1 % ascorbic acid. The rats were sacrificed at the 3rd, 5th, 10th and 20th day, respectively, after the injection of 6-OHDA. The cytotoxicity of 6-OHDA resulted in severe neurodegeneration of the dopaminergic neurons in the DRN. In the 3rd day, the dopaminergic fibers were dilated. In the 5th and 10th days, the dopaminergic fibers were depleted, and dopaminergic cell bodies were shrunken. In the 20th day, the dopaminergic cell bodies were almost completely disappeared. Astroglial reactions induced by 6-OHDA were also observed in the DRN. In the 5th day, astrocytes were significantly increased as compared with that of the control value. The value were reached at its maximum by the 20th day. Based on the present results, it suggests that 6-OHDA may act as a specific neurotoxin to dopaminergic neurons in the DRN, and induce severe neurodegenerative changes. Also, it suggests that the astroglial reaction in the DRN is gradually activated during the neurodegerative changes.

Cytotoxic Effect of 5, 7-DHT on the Endogenous Glial Cells in the Dorsal Raphe Nucleus of the Rat / 대한해부학회지

This study was designed to clarify the cytotoxic effects of 5, 7-dihydroxytryptamine (5, 7-DHT) on the serotonergic neurons in the dorsal raphe nucleus, and to investigate the glial reaction during the neurodegenerative changes by light and electron microscopy. Adult male rats (Sprague-Dawley strain) weighing from 250 g to 350 g each were used as experimental animal. 5, 7-DHT (200 mg dissolved in 0.9% NaCl) was injected into the lateral ventricle of the rat brain with the Hamiton syringe fixed on stereotaxic apparatus. The control rats were given with the similar volume of 0.9% NaCl. The rats were sacrified on the 1st, 3rd, 5th, 10th and 20th day after the injection of 5, 7-DHT. The results were as follows : Glial reactions induced by 5, 7-DHT were also observed in DRN. In early experimental stage, microglial reactions prevailed, whereas astroglial reactions were prevailing in later stage. In addition, microglial cells phagocytosed and removed the degenerated cells. However, astrocytes in DRN did not show phagocytotic activities such as microglial cells. Based on the results, author thought that 5, 7-DHT act as a specific neurotoxin to serotonergic neurons in DRN, and induces severe neurodegenerative changes. The glial reactions in DRN are activated during the neurodegerative changes, and show characteristic patterns of glial reactions.

Cytotoxic Effect of 5, 7-DHT on the Serotonergic Neurons in the Dorsal Raphe Nucleus of the Rat / 대한해부학회지

This study was designed to clarify the cytotoxic effects of 5, 7-dihydroxytryptamine (5, 7-DHT) on the serotonergic neurons in the dorsal raphe nucleus, and to investigate the glial reaction during the neurodegenerative changes by light and electron microscopy. Adult male rats (Sprague-Dawley strain) weighing from 250 g to 350 g each were used as experimental animal. 5, 7-DHT (200 microgram dissolved in 0.9% NaCl) was injected into the lateral ventricle of the rat brain with the Hamiton syringe fixed on stereotaxic apparatus. The control rats were given with the similar volume of 0.9% NaCl. The rats were sacrified on the 1st, 3rd, 5th, 10th and 20th day after the injection of 5, 7-DHT. The results were as follows : The cytotoxicity of 5, 7-DHT resulted in severe neurodegenerations of the serotonergic neurons. Most degenerated cells mainly showed necrotic findings, but a few of them exhibited apoptotic features. That is, in early stage of this experiment, the degenerated cells showed edematic changes of cytoplasm, but their nuclei were relatively seen intact. In late stage, the cells showed dark degenerative changes both in their cytoplasm and nuclei. Thereafter the cells were autolysed or phagocytosed by neighboring glial cells. Based on the results, author thought that 5, 7-DHT act as a specific neurotoxin to serotonergic neurons in DRN, and induces severe neurodegenerative changes. The glial reactions in DRN are activated during the neurodegerative changes, and show characteristic patterns of glial reactions.