Experiments were performed on SD rats. The animals were anesthetized with urethane (1. 0 g/kg, i. p. ). The diaphragmatic electric activity and intratracheal pressure were monitored. Morphine (4 mg/kg, i. v. ) caused ...Experiments were performed on SD rats. The animals were anesthetized with urethane (1. 0 g/kg, i. p. ). The diaphragmatic electric activity and intratracheal pressure were monitored. Morphine (4 mg/kg, i. v. ) caused marked respiratory inhibition. The respiratory frequency (RF), integrated diaphragmatic electric activity (IDEA) and diaphragmatic minute activity (DMA) were decreased. The respiratory depression effect of morphine was almost completely eliminated by pretreatment with naloxone injected into the medial areas of the nucleus retrofacialis (mNRF). Bilateral microinjection of morphine (5 μg) into mNRF might result in apnea in all animals. This effect could be fully prevented by injection of naloxone into mNRF in advance. The results suggest that there might be morphine receptors in the mNRF and they might play an important role in the respiratory inhibition induced by systemic administration of morphine.展开更多
BACKGROUND： Nikethamide, a respiratory center stimulant, is widely used in China. However, its effects on the central nervous system and medullary respiratory center remain poorly understood. OBJECTIVE： To investiga...BACKGROUND： Nikethamide, a respiratory center stimulant, is widely used in China. However, its effects on the central nervous system and medullary respiratory center remain poorly understood. OBJECTIVE： To investigate the influence of nikethamide on inspiratory neuron discharge in the medial region of the nucleus retrofacialis in neonatal rats, based on the observations addressing rhythmic respiratory discharge generated by the basic medullary respiratory center and various respiration neuron discharges in brain slices. DESIGN, TIME AND SETTING： A controlled, observational study utilizing in vitro neuroelectrophysiology was performed at the Department of Physiology in Southern Medical University between September and December in 2007. MATERIALS： Nikethamide was purchased from Sigma, USA; BL-420E biological signal collection and manaclement system was provided by Chengdu TME Technology, China.METHODS： Isolated medulla-spinal cord preparations were collected from neonatal Sprague Dawley rats, aged 1-3 days. Tissues were divided to include the medial region of the nucleus retrofacialis, ventral respiratory, and dorsal respiratory groups. Subsequently, modified Kreb＇s solution and 5 μg/mL nikethamide-containing modified Kreb＇s solution were consecutively perfused into the medial region of the nucleus retrofacialis in neonatal rat brain slices. MAIN OUTCOME MEASURES： Hypoglossal nerve root respiratory-related rhythmic discharge activities and inspiratory neuron discharges were recorded with an adsorption electrode and microelectrode. RESULTS Nikethamide resulted in prolonged inspiratory neuron discharge time, shortened respiratory cycle and expiratory time. Nikethamide intervention resulted in enhanced integral amplitude of some inspiratory neurons with no changes in discharge frequency or increased discharge frequency in remaining inspiratory neurons with no changes in integral amplitude. CONCLUSION： Nikethamide excites inspiratory neurons in the basic rhythmic respiration and medullary respiratory center, in addition to increased inspiratory neuron and neural network excitability.展开更多
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.展开更多
In the structure of brain the medial preoptic area (MPO) and ventromedial nucleus of hypothalamus (VMN)are the two parts where the estrogen receptors concentrate but have opposite effects on sexual behavior. Recently ...In the structure of brain the medial preoptic area (MPO) and ventromedial nucleus of hypothalamus (VMN)are the two parts where the estrogen receptors concentrate but have opposite effects on sexual behavior. Recently estrogen receptors have been known to be located in the locus coeruleus(LC), where noradrenergic(NE) fibres terminate in the hypothalamus arising from cell bodies. The discharge rate of NE-ergic neurons in LC can be increased by electrical stimulation of MPO in a female rat at estrus stage, and decreased at diestrus stage. These studies help us to infer that VMN might have some modulation influence on NE-ergic neurons in LC. In order to study the pattern activities展开更多
OBJECTIVE Dopamine(DA)plays important roles in Pavlovian conditioning by mediating reward,learning and motivation.While the conditioning stimulation(CS) is the most important inducement for reinstatement in addiction....OBJECTIVE Dopamine(DA)plays important roles in Pavlovian conditioning by mediating reward,learning and motivation.While the conditioning stimulation(CS) is the most important inducement for reinstatement in addiction.The present study investigated the specific role of the DA projections to nucleus accumbens(NAc) and medial prefrontal cortices(mPFC) from ventral tegmental area(VTA) in reinstatement induced by cue.METHODS(1)Optogenetic intracranial self-stimulation and reinstatement.DAT-Cre transgenic mice received an injection of adeno-associated viral vectors encoding channelrhodopsin2(ChR2) or control vector into the VTA resulting in the selective expression of these opsins in DA neurons.Then,we stimulated the VTA,NAc(core and shel) or mP FC [prelimbic cortex(PL) and infralimbic cortex(IL)] via an optical fiber.In the reinforcement test,the mice with ChR2 learned instrumental responses corresponding to the delivery of photostimulation into the VTA with multiple frequencies and during time;in the reinstatement phase,stimulation of the DA projections to NAc(core or shell) or mPFC(IL and PL) from VTA to induce reinstatement after 2 weeks of extinction of self-stimulation.(2)Reinstatement in cocaine self-administration.Virus encoding ChR2 or hM4 Di were injected into VTA of DAT-Cre transgenic mice.The mice with ChR2 and hM4 Di in DA neurons were trained to establish self-administration of cocaine.After 2 weeks of extinction,laser stimulation of the DA projections to NAc(core or shel) or mP FC(IL and PL) was conducted to induce reinstatement.After that,Clozapine was injected in NAc core to test the impacts of VTA-NAc core depression on the reinstatement induced by cue.(3) Photometry of VTA DA neurons in reinstatement.DAT-Cre transgenic mice were received an injection of AAV-DIO-Gcamp6 m into VTA.After cocaine self-administration and extinction,mice with Gcamp6 m were challenged by cue(paired with cocaine previously) and the photometry of VTA DA neurons was conducted during the reinstatement.RESULTS(1)The enhanced self-stimulation behavior was positive correlation with the stimulation of DA neurons in VTA according to the increasing frequency of stimulation and extent stimulation duration time.Furthermore,DA receptor antagonists significantly depressed the frequency curve.(2) Only stimulation of the projections to the NAc core from the VTA significantly induced reinstatement after extinction of self-stimulation,neither shell nor mPFC(PL or IL).(3) Depression of VTA-NAc core projection significantly inhibited the reinstatement induced by cue.(4) DA neurons in VTA were activated when the cue appeared during the period of reinstatement test.CONCLUSION Mesocorticolimbic DA system directly modulate the reinforcement dependant on DA receptor.The activity of DA neurons in VTA is necessary for cue induced relapse.Importantly,projections to NAc core from VTA perform the unique effects in reinstatement.展开更多
目的:探讨活性氧族(reactive oxygen species,ROS)在延髓面神经后核内侧区(the medial area of nucleus retrofacia-lis,mNRF)对呼吸节律调控的作用。方法:仿Suzue方法制作新生大鼠含有舌下神经根及mNRF的离体延髓脑片标本,以吸附电极...目的:探讨活性氧族(reactive oxygen species,ROS)在延髓面神经后核内侧区(the medial area of nucleus retrofacia-lis,mNRF)对呼吸节律调控的作用。方法:仿Suzue方法制作新生大鼠含有舌下神经根及mNRF的离体延髓脑片标本,以吸附电极记录舌下神经根呼吸节律性放电活动(respiratory rhythmic activity,RRA)作为呼吸活动的指标,采用全细胞膜片钳记录模式在mNRF同步记录呼吸神经元。分别观察特丁基氢过氧化物(t-butyl hydroperoxide,tBHP)、α-硫辛酸(-αlipoic acid,α-LA)对mNRF呼吸起步神经元及RRA的影响。结果:tBHP可显著使呼吸周期缩短、幅度增加,-αLA使呼吸周期延长、幅度降低;同时α-LA可使Cd2+非敏感性呼吸起步神经元动作电位周期显著延长,幅度降低,对Cd2+敏感性呼吸起步神经元无显著影响;voltage steps和ramps表明α-LA可抑制Cd2+非敏感性起步神经元的短暂性和持久性的钠电流。结论:ROS对RRA、Cd2+非敏感性起步神经元具有兴奋性作用,是通过调节钠电流而起作用的。展开更多
Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected wit...Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.展开更多
文摘Experiments were performed on SD rats. The animals were anesthetized with urethane (1. 0 g/kg, i. p. ). The diaphragmatic electric activity and intratracheal pressure were monitored. Morphine (4 mg/kg, i. v. ) caused marked respiratory inhibition. The respiratory frequency (RF), integrated diaphragmatic electric activity (IDEA) and diaphragmatic minute activity (DMA) were decreased. The respiratory depression effect of morphine was almost completely eliminated by pretreatment with naloxone injected into the medial areas of the nucleus retrofacialis (mNRF). Bilateral microinjection of morphine (5 μg) into mNRF might result in apnea in all animals. This effect could be fully prevented by injection of naloxone into mNRF in advance. The results suggest that there might be morphine receptors in the mNRF and they might play an important role in the respiratory inhibition induced by systemic administration of morphine.
基金the National Natural Science Foundation of China,No.30570670the Natural Science Foundation of Guangdong Province,No.5004714
文摘BACKGROUND： Nikethamide, a respiratory center stimulant, is widely used in China. However, its effects on the central nervous system and medullary respiratory center remain poorly understood. OBJECTIVE： To investigate the influence of nikethamide on inspiratory neuron discharge in the medial region of the nucleus retrofacialis in neonatal rats, based on the observations addressing rhythmic respiratory discharge generated by the basic medullary respiratory center and various respiration neuron discharges in brain slices. DESIGN, TIME AND SETTING： A controlled, observational study utilizing in vitro neuroelectrophysiology was performed at the Department of Physiology in Southern Medical University between September and December in 2007. MATERIALS： Nikethamide was purchased from Sigma, USA; BL-420E biological signal collection and manaclement system was provided by Chengdu TME Technology, China.METHODS： Isolated medulla-spinal cord preparations were collected from neonatal Sprague Dawley rats, aged 1-3 days. Tissues were divided to include the medial region of the nucleus retrofacialis, ventral respiratory, and dorsal respiratory groups. Subsequently, modified Kreb＇s solution and 5 μg/mL nikethamide-containing modified Kreb＇s solution were consecutively perfused into the medial region of the nucleus retrofacialis in neonatal rat brain slices. MAIN OUTCOME MEASURES： Hypoglossal nerve root respiratory-related rhythmic discharge activities and inspiratory neuron discharges were recorded with an adsorption electrode and microelectrode. RESULTS Nikethamide resulted in prolonged inspiratory neuron discharge time, shortened respiratory cycle and expiratory time. Nikethamide intervention resulted in enhanced integral amplitude of some inspiratory neurons with no changes in discharge frequency or increased discharge frequency in remaining inspiratory neurons with no changes in integral amplitude. CONCLUSION： Nikethamide excites inspiratory neurons in the basic rhythmic respiration and medullary respiratory center, in addition to increased inspiratory neuron and neural network excitability.
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
文摘In the structure of brain the medial preoptic area (MPO) and ventromedial nucleus of hypothalamus (VMN)are the two parts where the estrogen receptors concentrate but have opposite effects on sexual behavior. Recently estrogen receptors have been known to be located in the locus coeruleus(LC), where noradrenergic(NE) fibres terminate in the hypothalamus arising from cell bodies. The discharge rate of NE-ergic neurons in LC can be increased by electrical stimulation of MPO in a female rat at estrus stage, and decreased at diestrus stage. These studies help us to infer that VMN might have some modulation influence on NE-ergic neurons in LC. In order to study the pattern activities
基金National Key Research and Development (2016YFC0800907)Project 973 (2015CB553504)+1 种基金National Natural Science Foundation of China(81573405)Beijing Nova Program(xx2014A014).
文摘OBJECTIVE Dopamine(DA)plays important roles in Pavlovian conditioning by mediating reward,learning and motivation.While the conditioning stimulation(CS) is the most important inducement for reinstatement in addiction.The present study investigated the specific role of the DA projections to nucleus accumbens(NAc) and medial prefrontal cortices(mPFC) from ventral tegmental area(VTA) in reinstatement induced by cue.METHODS(1)Optogenetic intracranial self-stimulation and reinstatement.DAT-Cre transgenic mice received an injection of adeno-associated viral vectors encoding channelrhodopsin2(ChR2) or control vector into the VTA resulting in the selective expression of these opsins in DA neurons.Then,we stimulated the VTA,NAc(core and shel) or mP FC [prelimbic cortex(PL) and infralimbic cortex(IL)] via an optical fiber.In the reinforcement test,the mice with ChR2 learned instrumental responses corresponding to the delivery of photostimulation into the VTA with multiple frequencies and during time;in the reinstatement phase,stimulation of the DA projections to NAc(core or shell) or mPFC(IL and PL) from VTA to induce reinstatement after 2 weeks of extinction of self-stimulation.(2)Reinstatement in cocaine self-administration.Virus encoding ChR2 or hM4 Di were injected into VTA of DAT-Cre transgenic mice.The mice with ChR2 and hM4 Di in DA neurons were trained to establish self-administration of cocaine.After 2 weeks of extinction,laser stimulation of the DA projections to NAc(core or shel) or mP FC(IL and PL) was conducted to induce reinstatement.After that,Clozapine was injected in NAc core to test the impacts of VTA-NAc core depression on the reinstatement induced by cue.(3) Photometry of VTA DA neurons in reinstatement.DAT-Cre transgenic mice were received an injection of AAV-DIO-Gcamp6 m into VTA.After cocaine self-administration and extinction,mice with Gcamp6 m were challenged by cue(paired with cocaine previously) and the photometry of VTA DA neurons was conducted during the reinstatement.RESULTS(1)The enhanced self-stimulation behavior was positive correlation with the stimulation of DA neurons in VTA according to the increasing frequency of stimulation and extent stimulation duration time.Furthermore,DA receptor antagonists significantly depressed the frequency curve.(2) Only stimulation of the projections to the NAc core from the VTA significantly induced reinstatement after extinction of self-stimulation,neither shell nor mPFC(PL or IL).(3) Depression of VTA-NAc core projection significantly inhibited the reinstatement induced by cue.(4) DA neurons in VTA were activated when the cue appeared during the period of reinstatement test.CONCLUSION Mesocorticolimbic DA system directly modulate the reinforcement dependant on DA receptor.The activity of DA neurons in VTA is necessary for cue induced relapse.Importantly,projections to NAc core from VTA perform the unique effects in reinstatement.
文摘Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.
