OBJECTIVETo investigate the efferent pathway from the dorsal raphe nucleus to the inner ear.

METHODSEleven adult cats weighing 2.0 - 3.0 kg were used. The animals had no middle-ear disease and their auricle reflex was sensitive to sound. They were divided into experimental group (8 cats) and control group (3 cases). The fluorescent tracer cholera toxin subunit-B (CTB) was injected into cat cochlea and the CTB-labelled neurons of dorsal raphe nucleus (DRN) were identified using an immunofluorescence technique after a survival period of 7 days. For studying other fluorescence labelling, the sections containing CTB-labelled neurons were divided into four groups and incubated in antisera directed against tyrosine hydroxylase (TH), serotonin (5-HT), gamma-aminobutyric acid (GABA) and dopamine B-hydroxylase (DBH), respectively. Single-and double-labelled neurons were identified from the DRN.

RESULTS(1) A subpopulation of dorsal raphe nucleus (DRN) neurons were intensely labelled with CTB and these CTB-labelled neurons were densely distributed in a dorsomedial part of the DRN; (2) Four immunolabelling, TH, 5-HT, GABA and DBH were presented throughout the DRN. Of the total population of CTB-labelled neurons, 100% were TH-labelled neurons (double labelling) and no double-stained neuron with 5-HT, GABA and DBH was observed in the DRN.

CONCLUSIONSThere was a projection from DRN to the inner ear and this pathway might be a dopaminergic projection.

Animals ; Cats ; Ear, Inner ; innervation ; metabolism ; Efferent Pathways ; Neurons ; metabolism ; physiology ; Raphe Nuclei ; metabolism ; physiology

In the present study, changes of the neuronal activity of 5-hydroxytrypamine (5-HT) neurons of dorsal raphe nucleus(DRN) in a rat model of Parkinson's disease (PD) were investigated with glass microelectrode recording. The results showed that the discharge rates of 5-HT neurons in control and PD rats were (1.61+/-0.56) Hz and (2.61+/-1.97) Hz, respectively. The discharge rate of PD rats was significantly increased when compared to that of the control rats. In control rats, 79% of 5-HT neurons discharged regularly and 21% in bursts. In PD rats, however, 36% of 5-HT neurons discharged regularly, 16% irregularly and 47% in bursts. The percentage of 5-HT neurons discharging in bursts was obviously higher than that of the control rats (P<0.05). The data suggest that the discharge rate and bursting pattern of 5-HT neurons in DRN are increased in a rat model of Parkinson's disease.
Animals ; Electrophysiology ; Male ; Microelectrodes ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; Raphe Nuclei ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism

In this paper the response characteristic of the nerve fiber to the modulation magnetic field induction is studied by using the method of numeric simulation. It is found that the nerve fiber is sensitive to the low frequency modulated signal but not to the high frequency carrier wave. A simulative EEG signal generator is developed according to the change of EEG rhythm during the sleep. The simulative EEG square wave is modulated by high-frequency magnetic impulse. The modulation magnetic field is coupled into the rabbit's brain to study the influence of magnetic stimulation on the discharge of 5-hydroxytryptamine (5-HT) nerve cell. The experiment results demonstrate that discharge frequency of median raphe nuclei related to sleep changes significantly and the discharge becomes slow, which shows that magnetic stimulation can inhibit electrical activity of 5-HT nerve cell and provide a new way to improve insomnia.
Animals ; Brain ; metabolism ; physiology ; Computer Simulation ; Electroencephalography ; Electromagnetic Fields ; Electrophysiology ; Humans ; Neurons ; physiology ; Rabbits ; Raphe Nuclei ; metabolism ; physiology ; Serotonin ; metabolism ; Sleep ; physiology ; Sleep Initiation and Maintenance Disorders ; metabolism ; physiopathology

OBJECTIVETo investigate the relationship between serotonin (5-HT) and epilepsy and the mechanism of learning-memory in pilocarpine (PILO)-induced epileptic rats after 5,7-dihydroxytryptamine (5,7-DHT) microinjection in median raphe nucleus.

METHODSAdult S D rats were randomly divided into 3 groups: PILO group, PILO+ 5,7-DHT group, vehicle control group; PILO group was divided into two groups by status epilepticus (SE): PILO + SE group and PILO - SE group. The rats' seizures and cortex electroencephalography (EEG) were observed by video EEG. The rats' spatial learning-memory was evaluated by Morris water maze. Finally, serotonergic neuron in raphe nuclei was observed by immunohistochemistry.

RESULTSAfter treatment of 5,7-DHT (PILO + 5,7-DHT group), the success rate, the mortality and the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy model were all improved. Compared with the control group, the number of serotonergic neuron in raphe nuclei was decrease in PILO + SE group (P < 0.05). Moreover, it's extremely decrease in PILO + 5,7-DHT group (P < 0.01). Compared with control group, the mean escape latency was prolonged, the times of crossing target was decreased and the retention time in target zone was shortened in PILO + SE group (P < 0.05), but there was no significant difference between PILO + SE group and PILO + 5,7-DHT group.

CONCLUSIONDepletion of serotonin may facility the rats' epileptic seizures, but we could not interpret which may cause epileptic rats' cognitive deficit.

5,7-Dihydroxytryptamine ; toxicity ; Animals ; Epilepsy ; chemically induced ; metabolism ; psychology ; Male ; Maze Learning ; Memory ; Pilocarpine ; adverse effects ; Raphe Nuclei ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.
Animals ; Cell Proliferation/*drug effects ; *Dentate Gyrus/cytology/drug effects/metabolism ; Imidazoles/*pharmacology ; Male ; Phosphodiesterase Inhibitors/*pharmacology ; Piperazines/*pharmacology ; *Raphe Nuclei/cytology/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin/*biosynthesis ; Sulfones/pharmacology ; Triazines/pharmacology ; Tryptophan Hydroxylase/metabolism

AIMTo investigate the effect of CSF contacting neurons (CSF-CNs) lesion in rat dorsal raphe nucleus (DRN) on the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord, and study the relationship between the distal CSF-CNs in rat brain parenchyma and the development of morphine dependence and withdrawal.

METHODSChemical lesion of neurons the injection of cholera toxin subunit B with horseradish peroxidase (CB-HRP) into one of the rats lateral ventricles, TMBST reaction, nNOS immunohistochemistry and Western blot were used in this study.

RESULTSThe withdrawal symptoms by the naloxone precipitated attenuated obviously after the lesion of CSF-CNs in rat DRN, scores of all signs were significantly decreased about 38% compared to that of withdrawal group without lesion (P < 0.05). The withdrawal symptoms scores of vehicle withdrawal group and side lesion withdrawal group were not changed significantly (P > 0.05). Neurons in the location of CSF-CNs concentrated in the rat brain slices of lesion group were damaged obviously, there were only few CB-HRP positive neurons around the lesion location. But the location and the quantity of the CB-HRP positive neurons in the brain slices of the group without lesion was stable relatively, and their appearance was very clear. After the lesion, the nNOS expression and the quantity of the nNOS positive neurons in dorsal horn of spinal cord decreased significantly compared to that of withdrawal group without lesion (P < 0.05), but it also increased significantly compared to that of normal group and dependence group (P < 0.01).

CONCLUSIONThe lesion of distal CSF contacting neurons attenuated the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord. The distal CSF contacting neurons in rat brain parenchyma partly participated in the development of morphine dependence and naloxone precipitated withdrawal possibly by the modulation of NO (nitric oxide).

Animals ; Brain ; drug effects ; pathology ; Male ; Morphine Dependence ; metabolism ; Neurons ; drug effects ; pathology ; Nitric Oxide Synthase Type I ; metabolism ; Raphe Nuclei ; cytology ; pathology ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome ; metabolism

In the present study, changes in the neuronal activity of serotonergic neurons in the dorsal raphe nucleus (DRN) and the effect of the selective 5-HT(1A) receptor antagonist WAY-100635 in a rat model of Parkinson's disease (PD) were investigated by using extracellular single unit recording. Rat model of PD was produced by microinjection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta on the right side of the brain. The results showed that the mean spontaneous firing rate of DRN serotonergic neurons in the control and 6-OHDA-lesioned rats were (1.76+/-0.11) spikes/s (n=24) and (2.43+/-0.17) spikes/s (n=21), respectively. The firing rate of serotonergic neurons in 6-OHDA-lesioned rats was significantly higher than that in the control rats (P<0.001). In the control rats, 92% (22/24) of the neurons fired regularly and 8% (2/24) fired in bursts. In rats with 6-OHDA lesions, 9% (2/21) of neurons fired regularly, 43% (9/21) exhibited irregular pattern and 48% (10/21) fired in bursts. The percentage of DRN serotonergic neurons firing in bursts was obviously higher in 6-OHDA-lesioned rats than that in the control rats (P<0.001). Local injection of WAY-100635 (3 microg in 200 nL) into the DRN significantly increased the firing rate of serotonergic neurons with no change in firing pattern in the control rats (n=19, P<0.002), but did not change the firing rate and firing pattern of serotonergic neurons in 6-OHDA-lesioned rats (n=17, P>0.05). These results suggest the dysfunction of 5-HT(1A) receptor in 6-OHDA-lesioned rats and the involvement of the DRN in the pathophysiological mechanism of PD.
Action Potentials ; physiology ; Animals ; Disease Models, Animal ; Male ; Neurons ; physiology ; Oxidopamine ; Parkinsonian Disorders ; chemically induced ; physiopathology ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Raphe Nuclei ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Serotonin Antagonists ; pharmacology

By means of Fos immunocytochemistry, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and microinjection methods, the role of nitric oxide synthase (NOS) of dorsal raphe (DR) neurons in the modulation of rats sigmoid pain was studied. The results showed: (1) Rats exhibited aversive behavioral responses related to visceral pain after injecting formalin into the sigmoid wall. NOS neurons in DR were up-regulated, in addition, about 8% of NOS-labeled neurons were Fos positive. By contrast, there were no Fos/NOS double-labeled neurons in the control group. (2) Formalin-induced sigmoid pain scores and the expression of Fos in the spinal cord at S1 segment were decreased after microinjecting L-NAME into the DR. These findings suggest that NOS neurons are involved in the modulation of formalin-induced sigmoid pain and that NO may play an important role in the transmission of visceral nociceptive message in the midbrain.
Analgesics ; pharmacology ; Animals ; Genes, fos ; Microinjections ; NG-Nitroarginine Methyl Ester ; pharmacology ; Neurons ; physiology ; Nitric Oxide Synthase ; metabolism ; Nociceptors ; physiology ; Pain ; chemically induced ; physiopathology ; Pain Measurement ; Raphe Nuclei ; physiology ; Rats ; Rats, Sprague-Dawley ; Sigmoid Diseases ; chemically induced ; physiopathology

This study was conducted to determine if an oral squamous cell carcinoma alters mRNA expression of serotonin transporter (5-HTT) in the central nervous system. KB cell line derived from a human oral squamous cell carcinoma was inoculated into nude mice, and mRNA expression level of 5-HTT in the dorsal raphe nucleus (DRN) was examined by in situ hybridization when the tumor mass reached to -10% of total body weight. Plasma leptin levels were determined by radioimmunoassay method using a commercial kit. 5-HTT mRNA level was significantly decreased in the DRN of tumor bearing mice, compared to the age-matching non-tumor control. Plasma leptin level decreased concomitantly in tumor bearing mice. These results suggest that oral carcinoma may suppress 5-HTT gene expression in the central nervous system, perhaps in relation with decreased plasma leptin level.
Animals ; Body Weight ; Carcinoma, Squamous Cell/*metabolism/pathology ; DNA, Complementary ; *Gene Expression Regulation, Neoplastic ; Humans ; Leptin/blood ; Male ; Membrane Glycoproteins/*genetics/metabolism ; Membrane Transport Proteins/*genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mouth Neoplasms/*metabolism/pathology ; Nerve Tissue Proteins/*genetics/metabolism ; RNA, Messenger/*metabolism ; Radioimmunoassay ; Raphe Nuclei/*metabolism ; Research Support, Non-U.S. Gov't ; Serotonin/metabolism

OBJECTIVE: This study investigates the effects of chronic alcohol exposure on rat brain THmRNA expression, TH (tyrosine hydroxylase) acitivity, and TPH (tryptophan hydroxylase) activity which are important in synthesis of dopamine and serotonin and other components of both the dopaminergic and serotonergic systems of the rat brain. METHODS: Rats were fed a liquid diet containing alcohol for 4 weeks. We investigated effects of chronic alcohol exposure on dopaminergic systems as follows. We evaluated expression of THmRNA in LC, VTA and substantia nigra by using in-situ hybridization and measured activity of TH by using immunoassay. We used HPLC for simultaneous measurement of dopamine, DOPAC and HVA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. Also we investigated serotonergic systems as follows. We evaluated expression of TH mRNA in the dorsal raphe nucleus by using radioprobe and measured the activity of TPH by using enzyme immunoassay. We used HPLC for simultaneous measurement of 5-HT and 5-HIAA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. RESULTS: Alcohol exposure for 4 weeks increased the expression of TH mRNA in the ventral tegmental area and the locus ceruleus but not in the substantia nigra. The 4 weeks of alcohol exposure did not cause significant changes in levels of dopamine and metabolites in the different areas of the brain, nor was it associated with changes in the maximal binding and affinity (Kd) of anterior striatal dopamine D2 receptor. Alcohol exposure for 4 weeks had no effect on the expression of TPH mRNA or on the activity of TPH in the dorsal raphe nucleus and the hypothalamus. CONCLUSION: We reported at first that chronic alcohol exposure could increase TH mRNA in the locus ceruleus. In a previous study of acute alcohol treatment, there is increase of dopamine metabolism but in this study, we did not observe any changes in dopamine metabolism in the different areas of the brain. Also we did not see any significant changes in the synthesis and metabolism of serotonin after 4 weeks of chronic alcohol exposure compared with control. Therefore, synthesis and metabolism of serotonin was affected in the acute phase. And, as previous reports have suggested, any changes caused by alcohol returned to previous levels via adaptation and regulatory mechanisms.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain ; Cerebellum ; Cerebral Cortex ; Chromatography, High Pressure Liquid ; Diet ; Dopamine ; Hippocampus ; Hydroxyindoleacetic Acid ; Hypothalamus ; Immunoassay ; Immunoenzyme Techniques ; Locus Coeruleus ; Metabolism ; Raphe Nuclei ; Rats* ; Receptors, Dopamine D2 ; Rhombencephalon ; RNA, Messenger ; Serotonin ; Substantia Nigra ; Synaptic Transmission* ; Ventral Tegmental Area