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@#Introduction: Intracerebroventricular administration of streptozotocin (icv-STZ) induced apoptosis changes in neurons similar to Alzheimer's disease. The serotonergic system via its receptor involved in survival of neurons. The present study examined the ability of selective 5-HT1A receptor antagonist (NAD-299) and 5-HT2A receptor agonist (TCB-2) to attenuate the apoptosis caused by the icv-STZ in the rat. Methods: The icv-STZ (3 mg/kg, 10 μL, twice) induced neuronal loss in the hippocampus of adult male rats. Animals were divided into naive control, sham-operated, STZ+saline (1 μL, icv), STZ+NAD-299 (5 μg/μL, icv), STZ+TCB-2 (5 μg/μL, icv), and STZ+NAD-299+TCB-2 (5 μg/μL of any agent, icv) groups. Following the 35 days’ treatment period, neuronal apoptosis was detected using the Tunnel. Cells with morphological features of apoptotic cell were contended by microscopy. Results: TCB-2 and NAD-299 administration decreased number of apoptotic neurons in the treatment group compared with the STZ group. Combined treatment of STZ rat with NAD+TCB more decreased number of apoptotic cells in compare to TCB-2 or NAD-299 treated STZ groups. Conclusion: Treatment with 5-HT1A receptor antagonist or 5-HT2A receptor agonist diminished apoptosis. The beneficial effect of 5HT1A receptor inhibition was potentiated with activation of 5-HT2A receptor in prevention of apoptosis in hippocampus.
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Objective To explore the effect of serotonin 1A (5-HT1A) receptor agonist 8-OH-DPAT on pathological aggressive behavior, brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in prefrontal cortex and hippocampus in pubertal rats. Methods Forty-two 21-day-old male SD rats were randomly divided into 6 groups:model group, normal group, model+8-OH-DPAT group, model+normal saline (NS) group, normal+8-OH-DPAT group and normal+NS group, with 7 rats in each group. The rats in the model, model+8-OH-DPAT and model+NS groups were given a series of early chronic stresses to establish the pathological aggressive animal model, and the other 3 groups were fed normally. Then the rats in the model+8-OH-DPAT and normal+8-OH-DPAT groups were injected intraperitoneally with 8-OH-DPAT (0.5 mg/kg), while the rats in the model+NS and normal groups were administered with 2 mL of NS. We determined the aggressive behaviors of the rats through resident-intruder test and detected the protein expressions of BDNF and GDNF in prefrontal cortex and hippocampus by Western blotting. Results (1) Compared with the normal group, the latency in the first attack in the model group was significantly shorter (P0.05). (2) The protein expressions of BDNF and GDNF in the prefrontal cortex and hippocampus in the model group were significantly lower than those in the normal group (P<0.01), but they were significantly decreased in the model+NS group compared with the normal+NS group (P<0.05, P<0.01) and were significantly increased in the model+8-OH-DPAT group compared with the model+NS group (P<0.05, P<0.01). Conclusion The expressions of BDNF and GDNF in the prefrontal cortex and hippocampus may be related to the pathological aggressive behaviors induced by early chronic stress in puberty rats. 5-HT1A receptor agonist can reduce the pathological aggressive behaviors induced by early chronic stress and increase the expressions of BDNF and GDNF in prefrontal cortex and hippocampus in puberty rats.
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AIM: To investigate the change of long-term potentiation ( LTP ) , and the expression of 5-hydroxytryptamine 1A receptor (5-HT1A receptor) and postsynaptic density protein 95 (PSD-95) in the hippocampus of the rats with posttraumatic stress disorder (PTSD), and to explore the mechanism of 5-HT1A receptor in the regulation of spatial memory in the PTSD rats.METHODS:Healthy adult SD rats (n=36) were randomly divided into control group and mod-el group, with 18 rats in each group.The rats in model group were treated with single prolonged stress to construct the mod-el of PTSD.Morris water maze ( MWM) was used to test the learning and memory ability .The LTP induced by high-fre-quency stimulation (HFS) was detected by electrophysiological method .The protein expression of 5-HT1A receptor and PSD-95 in the hippocampus was determined by Western blot and immunofluorescence .RESULTS: The MWM analysis showed that the latency of the rats searching for the underwater platform in model group was significantly longer than that in control group (P<0.01).The results of electrophysiological analysis showed that the amplitude of the evoked potential in both groups were significantly increased after HFS in the hippocampus , but that in model group was significantly lower than that in control group (P<0.01).The results of Western blot and immunofluorescence analysis showed that compared with control group, the protein expression of 5-HT1A receptor was obviously increased (P<0.05), while the expression of PSD-95 was obviously decreased in model group (P<0.05).CONCLUSION:The spatial memory impairment in the PTSD rats may be associated with the increase in the expression of 5-HT1A receptor and the decrease in the expression of PSD-95 in the CA1 region of hippocampus .
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Objective To explore the efficacy of aripiprazole in patients with bipolar disorder D2 receptor and 5 -HT1A receptor partial agonists and analyze 5 -HT2A receptor antagonism.Methods From January 2013 to January 2015,113 patients came to our hospital for treatment of bipolar disorder,in accordance with the order of admission,were divide into aripiprazole group (47 cases)and control group (66 cases).The control group was given venlafaxine,aripiprazole group was given aripiprazole treatment on the basis of the control group.SDS,BRMS score and therapeutic effect were compared between the two groups before and after treatment.Results The SDS,BRMS scores were decreased after treatment in the two groups,compared with before treatment,the differences were statisti-cally significant (t =31.3587,36.1207;all P <0.05 );and the aripiprazole group decreased more significantly than the control group,the SDS,BRMS scores of the two groups after treatment had statistically significant differences [SDS (31.8 ±4.3)points vs (28.7 ±3.6)points,BRMS (6.5 ±0.2)points vs (5.5 ±0.2)points,t =4.110 7,26.197 0, all P <0.05 ].The total effective rate of the aripiprazole group was 97.9%,which was significantly higher than 89.4% of the control group (u =3.365 9,P =0.000 8).The incidence rate of adverse reactions such as nausea, vomiting,drowsiness,anxiety and heart rate in the aripiprazole group was significantly lower than the control group (all P <0.05 ).Conclusion Aripiprazole for bipolar disorder patients with D2 receptor and 5 -HT1A receptor has partial agonism,of 5 -HT2A receptor with role constraints,can effectively improve the effect of treatment of patients,reduce the incidence of adverse reactions.
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Objective: To observe the influence of Kaixin Powder on ethology, content of 5-HT in the hippocampus, expression of mRNA, and protein in 5-HT1A and 5-HT2A receptors in the hippocampus of depressed rats induced by chronic unpredictable mild stress (CUMS). Methods: Twenty-four male Wistar rats were randomly divided into blank, model, Trazodone, and Kaixin Powder groups, six rats in each group. In addition to the blank control group, other groups were established the depression model induced by CUMS combined with isolated feeding. At the same time, Trazodone group and Kaixin Powder group were treated with corresponding drugs for 3 weeks. After 3 weeks of administration, the rats were sacrificed, and a series of indexes were measured such as the contents of 5-HT, mRNA expression levels of 5-HT1A and 5-HT2A receptors, protein expression levels of 5-HT1A and 5-HT2A receptors, and so on. Results: A series of indexes in the model group were decreased significantly such as the body weight growth, the sugar water intake, the score of Open Field Test, the content of 5-HT in the hippocampus, expression of mRNA, and protein in 5-HT1A receptor, while the expression of mRNA and protein in 5-HT2A receptor were increased significantly. Compared with the model group, the indexes were ameliorated in Trazodone and Kaixin Powder groups. Kaixin Powder is better than Trazodone in decreasing the level of protein in 5-HT2A receptor. Conclusion: The result indicated that the depression performance of depressed rats induced by CUMS can be ameliorated by Kaixin Powder, and the mechanism maybe concerned with increasing the contents of 5-HT, exciting 5-HT1A receptor, and antagonising 5-HT2A receptor.
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Objective To explore the influence of intraventricular injection of 5, 7-drhydroxytryptamine (5, 7-DHT)in 5-HT1A receptor sensitivity of medial prefrontal cortex pyramidal neurons in the rats,and to clarity the effect of 5-HT1A receptor on the eletronic response of pyramidal neurons.Methods 36 male SD rats were randomly divided into sham operation group (n=21)and 5,7-DHT lesion group (n=15).5,7-DHT was injected intraventricularly in the rats in 5,7-DHT lesion group,and the same dose saline was injected in the rats in sham operation group.The rats in two groups were intravenously injected with different doses(0.5-128.0μg·kg-1 )of 8-CH-DPAT.The firing rate of mPFC pyramidal neurons was recorded with extracellular electrophysioological examination.The rats in two groups were intravenously injected with WAY100635,the sensitivites of the rats to 8-OH-DPAT and WAY100635 in 5, 7-DHT lesion group were observed, and compared with sham operation group.Results The different doses (0.5-128.0μg·L-1 )of 8-OH-DDAT had an excitatory-inhibitory effect on the firing rate of mPFC pyamidal neurons in sham operation group;the neurons were excited when the doses of 8-OH-DPAT were 0.5-38.0μg·kg-1 ,and the firing rates were increased(P<0.05);the neurons were inhibited when the dose of 8-OH-DPAT was 128.0μg·kg-1 ,and the firing rate was decreased.The different doses(0.5-218.0μg·L-1 )of 8-OH-DPAT inhibited the elecctronic response of pyramidal neurons of the rats in 5,7-DHT lesion group in a dose-dependent manner (df=5,F=3.44,P=0.003),and the firing rates were reduced. WAY-100635 (50μg·kg-1 )reversed completely the inhibition of 8-OH-DPAT.Conclusion The sensitivity of 5-HT1A receptor of rat mPFC pyramidal neurons can be decreased by intraventricular injection of 5,7-DHT.
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OBJECTIVE: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. METHODS: One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). RESULTS: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. CONCLUSION: Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.
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Humans , Antidepressive Agents , Counseling , Depression , Depressive Disorder, Major , Genotype , Psychotherapy , Receptor, Serotonin, 5-HT1A , Receptor, Serotonin, 5-HT2A , Serotonin , Serotonin Plasma Membrane Transport ProteinsABSTRACT
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.
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Animals , Male , Rats , Molsidomine/analogs & derivatives , Motor Activity/drug effects , Nitric Oxide/pharmacology , Raphe Nuclei/drug effects , /drug effects , /pharmacology , Dose-Response Relationship, Drug , Glycine/analogs & derivatives , Glycine/pharmacology , Molsidomine/pharmacology , Motor Activity/physiology , Rats, WistarABSTRACT
Objective: To evaluate the antidepressant-like effect on animal models of a novel compound YL-0919, a dual 5-HT1A agonist and serotonin reuptake inhibitior. Methods: Using the tail suspension test, the forced swimming test and the locomotor activity test in mice, and the learned helplessness test in rats,the antidepressant-like effect of YL-0919 (0.625,1.25,2.5 and 5.0 mg/kg) were evaluated. Results: In the tail suspension test and the forced swimming test in mice, intragastric administration of YL-0919 (0.625-2.5 mg/kg) significantly decreased the immobility time. And in this dose range YL-0919 did not influence the locomotor activity in mice. In the learned helplessness test in rats,YL-0919 (0.625-1.25 mg/kg per day,once a day for 4 days) significantly decreased the numbers of escape failure. Conclusion: YL-0919 produced reliable antidepressive effect on the three animal models in the dose without stimulant or inhibitive effect on behaviors. And no excite or inhibition effect of YL-0919 on central nerve systems was observed. These results suggest that YL-0919 have the potential foreground as a novel antidepressant.
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Growing evidence indicates that the serotonin system is important in learning and memory. In particular, several preclinical and clinical studies suggest that modulating the 5-HT1A receptor can influence learning and memory, and indeed, it has been observed that presynaptic 5-HT1A receptor agonists and postsynaptic 5-HT1A receptor antagonists tend to ameliorate the learning/memory impairment induced by various methods. In contrast, post-synaptic 5-HT1A receptor agonists tend to decrease the learning/memory function. These observations suggest the possibility that modulating neurotransmission mediated by the 5-HT1A receptor may be effective as a therapeutic strategy for enhancing learning and memory in various neuropsychiatric disorders. Unfortunately, there is no available discussion on the relationship between 5-HT1A receptor and learning/memory in Korea. This article reviews the clinical or preclinical literature on this issue.
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Korea , Learning , Memory , Receptor, Serotonin, 5-HT1A , Serotonin , Synaptic TransmissionABSTRACT
Developmental disability shows life-long behavioral abnormality with no significant physical malformation. This study was undertaken to develop an animal model for developmental disability by using two-factor approach. Lipopolysaccharide (LPS), a bacterial toxin, and NAN-190, a 5-HT1A receptor antagonist, were administered to Sprague-Dawley rats on postnatal day (PND) 5 to induce inflammation and an altered 5-HT system, respectively. Long-term alteration of behavior occurred in the drug-treated groups. The LPS-treated group showed impaired motor coordination in the Rota-rod test. The LPS- treated or both LPS and NAN-190-treated groups showed impaired fore-paw muscle power in the wire maneuver test. These groups also showed decreased white matter volume and increased serotonergic fibers. The LPS and NAN-190-treated group also exhibited neurologic deficit in the placing reaction test and impaired equilibrium function in the tilt table test. The results showed that a variety of altered behaviors can be generated by two factor model, and suggested that combination of important etiologic factors and possible underlying defects is a promising strategy of establishing an animal model for developmental disabilities.
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Animals , Developmental Disabilities , Inflammation , Models, Animal , Neurologic Manifestations , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT1A , Serotonin , Tilt-Table TestABSTRACT
5-HT(1A) receptor is implicated in the pathogenesis and the therapeutic mechanism of various psychiatric disorders. Especially, the mechanism of action of selective serotonin reuptake inhibitors (SSRIs) was hypothesized that 5-HT(1A) autoreceptor desensitization plays an important role in the treatment of depression and anxiety. 5-HT(1A) receptor stimulation may also mediate the neurogenesis of prefrontal cortex and hippocampus. The 5-HT(1A) agonism has an important meaning in the treatment of schizophrenia. Most atyptical antipsychotics have the property of 5-HT(2A) antagonist, and some have that of 5-HT(1A) agonist. In the various regions of brain, 5-HT(1A) and 5-HT(2A) have the functionally antagonistic properties. Recently, 5-HT(1A) receptor-related agents have been investigated in the treatment of acute ischemic stroke and Alzheimer's disease. Therefore, the further understanding about the 5-HT(1A) receptors in the brain functions will provide the development of future drugs and the advancement of psychopharmacology.
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Alzheimer Disease , Antipsychotic Agents , Anxiety , Autoreceptors , Brain , Depression , Drug Therapy , Felodipine , Hippocampus , Neurogenesis , Prefrontal Cortex , Psychopharmacology , Receptor, Serotonin, 5-HT1A , Schizophrenia , Serotonin , Selective Serotonin Reuptake Inhibitors , StrokeABSTRACT
0. 05) . Compared with Iso analgesic group ( Iso group) ,the TFL or HPPT of co-administration groups ( Iso + M6 group,Iso + M3 group) shortened ( P 0. 05) . Conclusion These findings suggest that the surface analgesic effects of Iso are closely related to the excited 5-HT1A receptor in the spinal cord of mice.
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Immunocytochemical staining technique by using specific antibody against 5-HT1A receptor subtype (5-HT1AR) wasused to observe the distribution of 5-HT1AR immunoreactivity in the rat nervous system. The highest level of 5-HT1AR im-munoreactivity was observed in piriform cortex, septum, ventraldorsal thalamic nucleus, reticular thalamic nucleus, basolateralamygdaloid nucleus, Purkinje cell layer, red nucleus, facial nucleus and nucleus of the trapezoid body. Considerably weaker im-munoreactivity was detected in hippocampus, frontal cortex, mediodorsal thalamic nucleus, interpeduncular nucleus, mesen-cephalic trigeminal nucleus, dorsal raphe nucleus, spinal trigeminal nucleus, the superficial layers of the spinal dorsal horn, dor-sal root and trigeminal nerve ganglia, Very weak immunoreactivity was found in the olfactory bulb, caudate putamen,globus pal-lidus, nucleus diagonal band, bed nucleus stria terminalis, habenular nucleus, substantia nigra and superior olive. The presentresults indicate that 5-HT1AR immunoreactive structures are widely distributed in the rat nervous system and might play impor-tant role in mediating the multiple effects of 5-HT in the nervous system.
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The role of 5-hydroxytryptamine (5-HT)1A receptor activity in prenatal ischemia was studied, by injecting 8-hydroxy-dipropylaminotetraline (8-OH-DPAT; 50 microgram/kg, s.c.), a 5-HT1A agonist on gestation day 17, and 30 min later inducing transient ischemia by ligating the uterine vessels for 30 min. On postnatal day 95, rats that had experienced prenatal ischemia showed impaired motor coordination and reduced concentration of 5-HT in the cerebellum compared with Sham-operated controls. In addition, they showed increased 5-HT1A receptor densities in the cerebral cortex. Pretreatment with 8-OH-DPAT ameliorated the behavioral and neurochemical sequelae measured in the present study. The results suggest that 5-HT1A receptors protect the brain from ischemic insult and/or facilitate recovery after prenatally experienced ischemia.
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Animals , Pregnancy , Rats , 8-Hydroxy-2-(di-n-propylamino)tetralin , Brain , Cerebellum , Cerebral Cortex , Ischemia , Neuroprotective Agents , Receptor, Serotonin, 5-HT1A , Serotonin , Serotonin 5-HT1 Receptor AgonistsABSTRACT
OBJECTIVES: The purpose of this study was to evaluate the prolactin and cortisol responses to 5-HT 1A receptor activation by buspirone in alcoholics. METHODS: The subjects were twenty two male alcoholic patients meeting the DSM-IV criteria for alcohol dependency and abstaining for more than 3 months. Patients were free from overt anxiety and depressive symptoms. Controls were fifteen male normal volunteers, with no psychiatric and medical illness. Blood samples for the measurement of serum cortisol and prolactin levels were drawn 0, 30, 60, 90, 120, 150 minutes after oral administration of 30mg buspirone hydrochloride at 9:00 a.m. RESULTS: The baseline cortisol levels were not significantly different between alcoholics and controls. Serum cortisol levels of controls after buspirone administration were significantly increased over time(p<0.01), but those of alcoholics did not increased. After 60 minutes following buspirone administration, cortisol levels were significantly lower in alcoholics than in controls(p<0.05). Prolactin responses to buspirone were not significantly different between the two groups. CONCLULSION: Our results suggested that 5-HT 1A receptor function is decreased in alcoholic patients.
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Humans , Male , Administration, Oral , Alcoholics , Alcoholism , Anxiety , Buspirone , Depression , Diagnostic and Statistical Manual of Mental Disorders , Healthy Volunteers , Hydrocortisone , Prolactin , SerotoninABSTRACT
BACKGROUND AND PURPOSE: Neurobehavioral teratology is a term used for the postnatal effects on behavior of prenatal exposure to drug or to specific environment. Perinatal hypoxia is a major risk factor for development of behavioral abnormalities, such as cerebral palsy, mental retardation and learning disability. The objective of this study is to investigate the effects of neonatal hypoxia on long-term changes of behavior and neurochemical system and to learn the role of 5-hyroxytryptamine(5-HT) in hypoxic stress. METHODS: Sprague-Dawley rats were grouped by hypoxia and/or 5-HT receptor antagonist treatment. Exposure to 100% N2 gas was done in postnatal day(PND) 2 for 12 minutes. NAN-190 HBr or ketanserin tartrate or both were injected intraperitoneally 30 minutes before exposure to hypoxic environment. Rats were weighed periodically and examined the eye opening. Wire maneuver test was done on PND 22. Between PND 40-55 and PND 63-84, explorative behavior test and Rota-Rod test were done serially. They were sacrificed in PND 100, and aminergic neurotransimitters and their metabolites were measured by High Performance Liquid Chromatography - Electrochemical Detection(HPLC ECD) system. Receptor binding assay was done using 8-OH-DPAT and ketanserin HCl in brain cortex. RESULTS: The group treated with 5-HT receptor antagonist and hypoxia showed higher death rate than 5-HT receptor antagonist or hypoxia alone. There were no differences in weight gain, eye opening, and the result of wire maneuver test among each groups. In explorative behavior test, NAN+N2 group in male and NAN group in female showed markedly increased activities. In Rota-Rod test, NAN and NAN+N2 groups in both male and female showed decreased motor coordination. There were no differences in the concentration of aminergic neurotransmitters and their metabolites, when measured in PND 100 according to the brain sites. There were no differences in pKd of 5-HT receptors measured on PND 100. But Bmax of 5-HT1A receptor were low in N2, NAN and NAN+N2 groups. NAN and NAN+N2 groups showed elevated Bmax of 5-HT2A/2C receptor. CONCLUSION: Exposure to hypoxia in neonatal period causes long-lasting neurobehavioral changes with neurochemical abnormalities, and 5-HT receptor activity has a role in that mechanism.
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Animals , Female , Humans , Infant, Newborn , Male , Rats , 8-Hydroxy-2-(di-n-propylamino)tetralin , Hypoxia , Brain , Cerebral Palsy , Chromatography, Liquid , Intellectual Disability , Ketanserin , Learning Disabilities , Mortality , Neurotransmitter Agents , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT1A , Receptors, Serotonin , Risk Factors , Serotonin , Teratology , Weight GainABSTRACT
Objective: To observe the effect of urapidil (agonist of 5-HT 1A receptor ) on morphine withdrawal syndrome Method: A physical dependent model in mice was established by subcutaneous injection of quantitative morphine The intensity of withdrawal syndrome was evaluated by observing jumping latency, jumping times and lose of body weight after intraperitoneal injection of naloxone (5 mg/kg) The effect of urapidil was observed after intraperitoneal injection it with 3 different dosages (100, 200, 400 mg/kg) Contents of NO in plasma and brain tissue were measured by nitrate reduction method Results: Morphine withdrawal syndrome was inhibited by urapidil at any dosage Content of NO in brain tissue reduced by urapidil 400 mg/kg, while plasma NO increased Conclusion: Urapidil inhibits morphine withdrawal syndrome in mice, increase the content of NO in their brain tissue
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Objective To observe the relationship between 5-Hydroxytryptamine(5-HT)-like immunoreactive terminals and the vestibulo-parabrachial nucleus projection neurons which may express 5-HT1A receptor in the vestibular nuclear complex(VNC). Methods Retrograded-tract tracing technique combined with double labeling of immunofluorescence histochemical was used,and the stained sections were observed under a confocal laser-scanning microscope. Results Following injection of tetramethylrhodamine(TMR) into the parabrachial nucleus, many retrogradely labeled neurons were observed bilaterally within VNC,but with an ipsilateral predominance.Immunofluorescence histochemical staining showed that many neurons expressed(5-HT1A) receptor-like immunoreactivity and a large number of 5-HT immunostained fibers or terminals were found in the medial,spinal,superior,lateral vestibular nucleus(MVe,SpVe,SuVe,LVe),X nucleus and Y nucleus.Confocal laser-scanning microscopy revealed that some TMR-labeled neurons were 5-HT_1AR immunopositive,and some of the cell bodies or dendrites of TMR/5-HT1AR double-labeled neurons were closely apposed by 5-HT-like immunoreactive terminals.Conclusion The present study suggests that 5-HT may modulate vestibular signals along the VNC-parabrachial nucleus pathway via 5-HT1A receptor.