RESUMO
INTRODUCTION: The effect of ethnicity on the efficacy of salmeterol (S)+fluticasone propionate (FP) has not been examined in Japanese and Caucasian asthmatics. In this study, the efficacy of combination treatment with S and FP from a single inhaler (SFC) was compared with concurrent treatment with S and FP administration from separate inhalers (S+FP) in Japanese and Caucasian asthmatics. METHODS: This was a randomised, double-blind, crossover study in male and female Japanese (n=18) and Caucasian (n=17) asthmatics (50-100% predicted FEV(1); >35% reversibility in sGaw). Subjects received SFC (S 50 mcg/FP 250 mcg b.i.d.) and S+FP (S 50 mcg b.i.d.+FP 250 mcg b.i.d.) for 14 days. sGaw and FEV(1) were determined 0-12h after the first and last doses. RESULTS: Treatment with both SFC and S+FP produced marked bronchodilation, which was maintained 0-12h after the first dose. Baseline sGaw and FEV(1) increased up to 51% and 180 mL, respectively, in Japanese subjects over 2 weeks of treatment, with similar improvements in Caucasian subjects. On Day 14 the 0-12h S+FP:SFC treatment ratios (90% CI) for sGaw AUC and peak were 1.05 (0.98, 1.12) and 1.05 (0.97, 1.14), respectively, in Japanese subjects, and 0.99 (0.92, 1.07) and 0.98 (0.89, 1.07), respectively, in Caucasian subjects, with no difference between the two ethnic groups. CONCLUSIONS: The finding of a similar significant bronchodilator response in Japanese and Caucasian asthmatics following concurrent and combination treatment with salmeterol and FP suggests that the therapeutic response to these agents is comparable and independent of ethnicity in Japanese and Caucasian asthma patients.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/análogos & derivados , Androstadienos/uso terapêutico , Asma/tratamento farmacológico , Asma/etnologia , Adolescente , Adulto , Idoso , Resistência das Vias Respiratórias , Albuterol/uso terapêutico , Análise de Variância , Antiasmáticos/uso terapêutico , Povo Asiático , Asma/fisiopatologia , Estatura , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Fluticasona , Combinação Fluticasona-Salmeterol , Humanos , Japão , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Testes de Função Respiratória , Xinafoato de Salmeterol , Suécia , Resultado do Tratamento , População BrancaRESUMO
Therapeutic equivalence between procaterol hydrochloride dry powder inhaler (Meptin DPI) and procaterol hydrochloride metered-dose inhaler (Meptin MDI), the currently marketed formulation, was assessed in 16 patients with bronchial asthma. The study was conducted in a randomized, double-dummy, double-blind crossover manner, using forced expiratory volume in the first second (FEV1) as an index of bronchodilatory effect. In Period I, the patients received 20 mcg of either Meptin DPI or Meptin MDI, and then crossed over in Period II after a washout interval of 3--28 days. Pharmacodynamic equivalence was accessed using AUC (FEV1)/h and peak FEV1 as indices, and the data were analyzed by analysis of variance (ANOVA). Factors used for the analysis were the treatment group and/or carryover effect, patients within each group, period, and treatment. The 90% confidence intervals for the differences between the two treatments were --0.0995 to --0.0204 (L) for mean AUC (FEV1)/h and --0.102 to --0.022 (L) for mean peak FEV1, both within the acceptance criteria of --0.15 to 0.15 (L). Meptin DPI was therefore assessed as being equivalent to the current Meptin MDI.
Assuntos
Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Inaladores Dosimetrados , Nebulizadores e Vaporizadores , Procaterol/administração & dosagem , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacocinética , Adulto , Idoso , Poluição do Ar/prevenção & controle , Broncodilatadores/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Pós , Procaterol/farmacocinética , Equivalência TerapêuticaRESUMO
Equivalence between a CFC-free procaterol hydrochloride metered-dose inhaler using HFA-227 as a propellant (Meptin [HFA]) and a CFC-containing procaterol hydrochloride metered-dose inhaler (Meptin [CFC]) was assessed in 28 patients with bronchial asthma. The study was conducted in a randomized, double-dummy, double-blind crossover manner, using forced expiratory volume in the first second (FEV1) as an index of bronchodilatory effect. In Period I, the patients received 20 microg of either Meptin [HFA] or Meptin [CFC] and then crossed over in Period II after a washout interval of 3-28 days. Pharmacodynamic equivalence was assessed using AUC (FEV1)/h and peak FEV1 as indices, and the data was analyzed by analysis of variance. Factors used for the analysis were the treatment group and/or carryover effect, patients within each group, period, and treatment. The 90% confidence intervals for the differences between the two treatments were -0.0507 to 0.0039 (L) for mean AUC (FEV1)/h and -0.056 to 0.026 (L) for mean peak FEV1, both within the acceptance criteria of -0.15 to 0.15 (L). Meptin [HFA] was therefore assessed as being equivalent to the current Meptin [CFC].
Assuntos
Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Clorofluorcarbonetos , Inaladores Dosimetrados/normas , Procaterol/administração & dosagem , Procaterol/farmacocinética , Administração por Inalação , Propelentes de Aerossol/administração & dosagem , Propelentes de Aerossol/farmacologia , Clorofluorcarbonetos/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Hidrocarbonetos Fluorados/administração & dosagem , Hidrocarbonetos Fluorados/farmacologia , Masculino , Pessoa de Meia-Idade , Equivalência TerapêuticaRESUMO
The present study was an attempt to elucidate the effects of avermectin B1a (AVM) and picrotoxin, an anion channel opener and blocker, respectively, on the release of endogenous dopamine from the slices of caudate nucleus of the rat, using a superfusion method in order to determine the interaction between these agents with the gamma-aminobutyric acid (GABA) receptor-anion channel complex. Avermectin (1.14-11.4 microM) reduced the Ca2+-dependent release of dopamine stimulated by 40 mM KCl without affecting the basal release of dopamine. In contrast, picrotoxin in doses larger than 20 microM facilitated the K+-stimulated release of dopamine. The inhibitory effect of avermectin was completely antagonized by 10 microM picrotoxin and 0.1 mM bicuculline; these doses of both agents did not change the K+-stimulated release of dopamine. Replacement of chloride (Cl-) in the superfusion medium with nitrate (NO3-) markedly facilitated the K+-stimulated release of dopamine and the increase was antagonized by verapamil (10 microM) and tetrodotoxin (1 microM). In the nitrate medium, avermectin reduced the K+-stimulated release of dopamine and the inhibitory effect was antagonized by bicuculline. However, picrotoxin up to 100 microM did not affect the K+-stimulated release of dopamine either in the presence or absence of bicuculline. These results suggest that the dopaminergic nerve terminals in the caudate nucleus receive inhibitory regulation through the facilitation of anion channels. This regulation is apparently altered depending on the main anion in the extracellular fluid.
Assuntos
Aminoácidos Neutros , Cloretos/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Ivermectina/análogos & derivados , Lactonas/farmacologia , Nitratos/metabolismo , Picrotoxina/farmacologia , Aminoácidos/farmacologia , Animais , Bicuculina/farmacologia , Dopamina/fisiologia , Técnicas In Vitro , Masculino , Ratos , Ratos Endogâmicos , Tetrodotoxina/farmacologia , Verapamil/farmacologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
Microiontophoretic experiments were performed to determine whether inhibition mediated by the ventral tegmental area neurons of the nucleus accumbens, receiving input from the parafascicular nucleus of thalamus, is mediated by dopamine D1 or D2 receptors, using rats anesthetized with chloral hydrate. Spikes, elicited by test stimuli applied to the parafascicular nucleus were inhibited by conditioning stimuli to the ventral tegmental area, given 30 msec before the test stimuli. This inhibition was antagonized by iontophoretic application of SCH 23390, a D1 antagonist, in 18 of 25 neurons of the nucleus accumbens, but in only 3 of 22 neurons of the nucleus accumbens during application of domperidone, a D2 antagonist. The reduction by conditioning stimulation of the ventral tegmental area of the mean number of spikes of the 25 neurons upon stimulation of the parafascicular nucleus, was abolished by SCH 23390. In contrast, domperidone did not affect the mean number of spikes of the 22 neurons upon stimulation of the parafascicular nucleus in the presence of conditioning stimulation of the ventral tegmental area. In addition, spikes elicited by stimulation of the parafascicular nucleus were dose-dependently inhibited by iontophoretic application of both SKF 38393, a D1 agonist and bromocriptine, a D2 agonist. These results suggest that inhibition by dopamine, derived from the ventral tegmental area of neurons of the nucleus accumbens, receiving input from the parafascicular nucleus, is mediated mainly by dopamine D1 receptors, although both D1 and D2 receptors are expressed on the same neuron of the nucleus accumbens, which is also inhibited by exogenously applied D2 agonists.
Assuntos
Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Receptores Dopaminérgicos/fisiologia , Núcleos Septais/fisiologia , Tegmento Mesencefálico/fisiologia , Núcleos Talâmicos/fisiologia , Animais , Benzazepinas/farmacologia , Bromocriptina/farmacologia , Domperidona/farmacologia , Estimulação Elétrica , Eletrocardiografia , Iontoforese , Masculino , Núcleo Accumbens/citologia , Núcleo Accumbens/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
Studies were performed to elucidate the effects of brotizolam, a newly synthesized thienodiazepine, chemically related to the benzodiazepines, on dopamine turnover in the limbic forebrain and neostriatum. Intraperitoneally administered brotizolam retarded the rate of alpha-methyl-p-tyrosine-induced depletion of dopamine in the olfactory tubercle (OT), nucleus accumbens (NA) and caudate nucleus (CN). Significant retardation was observed with brotizolam in doses ranging from 0.1-10 mg/kg in the olfactory tubercle, and from 1-10 mg/kg in the nucleus accumbens and caudate nucleus. These inhibitory effects of brotizolam were antagonized by bicuculline, a GABA antagonist, in all of the regions examined. Using slices of the olfactory tubercle, nucleus accumbens and caudate nucleus, the effects of brotizolam on dopaminergic nerve terminals were examined in vitro. Basal release of dopamine was not affected by brotizolam in concentrations up to 10(-6) M; however, K+-stimulated release of dopamine was significantly reduced by brotizolam at 10(-7) M or above. The reduction of K+-stimulated release of dopamine was antagonized by bicuculline, added in the superfusion medium. These data suggest that brotizolam inhibits the release of dopamine in the limbic forebrain and neostriatal systems probably through mechanisms including a facilitation of GABAergic action on dopaminergic nerve terminals.
Assuntos
Azepinas/farmacologia , Núcleo Caudado/efeitos dos fármacos , Dopamina/fisiologia , Sistema Límbico/efeitos dos fármacos , Putamen/efeitos dos fármacos , Animais , Bicuculina/farmacologia , Técnicas In Vitro , Masculino , Núcleo Accumbens/efeitos dos fármacos , Bulbo Olfatório/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The effects of thyrotropin-releasing hormone (TRH) were examined on neuronal activity in the nucleus accumbens, receiving an input from the parafascicular nucleus of the thalamus or the hippocampus, in chloral hydrate-anesthetized rats, using a microiontophoretic technique. The spikes produced by stimulation of the parafascicular nucleus were predominantly and dose-dependently inhibited during iontophoretic application of TRH. When the effects of TRH and dopamine were tested on the same neurons of the nucleus accumbens, inhibition of the generation of spikes by both drugs was observed in most neurons. In contrast, spikes elicited by stimulation of the hippocampus in most neurons of the nucleus accumbens were not affected by TRH or dopamine. Both TRH- and dopamine-induced inhibition of the spikes induced by stimulation of the parafascicular nucleus was antagonized by simultaneous application of haloperidol. In animals treated with reserpine, inhibition of the generation of spikes upon stimulation of the parafascicular nucleus did not occur in any neurons in the nucleus accumbens during application of TRH, whereas the dopamine-induced inhibition was still observed. These results suggest that inhibitory effects of TRH on the neurons of the nucleus accumbens receiving an input from the parafascicular nucleus are mediated by dopamine released from the dopaminergic nerve terminals located in the nucleus accumbens.
Assuntos
Inibição Neural , Neurônios/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Dopamina/farmacologia , Estimulação Elétrica , Eletrofisiologia , Haloperidol/farmacologia , Hipocampo/fisiologia , Masculino , Inibição Neural/efeitos dos fármacos , Neurônios/fisiologia , Núcleo Accumbens/citologia , Ratos , Reserpina/farmacologia , Núcleos Talâmicos/fisiologiaRESUMO
Electrophysiological studies, using chloral hydrate-anesthetized rats, were undertaken to determine whether hippocampal pyramidal neurons, receiving input from the medial septal nucleus, were affected by 5-hydroxytryptamine (5-HT) derived from the dorsal raphe nucleus. The pyramidal neurons in the CA1 region of the hippocampus were classified into short- and long-latency neurons, based on their response to stimulation of the medial septal nucleus. Microiontophoretically applied atropine inhibited the generation of spikes upon stimulation of the medial septal nucleus in short-latency neurons, but had no effect on long-latency neurons. In the short-latency neurons, the stimulation-induced spikes of the medial septal nucleus were inhibited by conditioning stimuli applied to the dorsal raphe nucleus and iontophoretic application of 5-HT and the 5-HT1A agonists, SM-3997 (3 a alpha,4 beta,7 beta,7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate) and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin). The conditioning effect of the dorsal raphe nucleus was antagonized by methysergide. However, in the long-latency neurons, the spikes elicited by stimulation of the medial septal nucleus were not affected by the conditioning stimulation of the dorsal raphe nucleus, or iontophoretically applied 5-HT. These results indicate that 5-HT, originating in the dorsal raphe nucleus inhibited hippocampal pyramidal neurons receiving cholinergic input from the medial septal nucleus, but not those receiving non-cholinergic input from the medial septal nucleus. The drug SM-3997 inhibited the activity of hippocampal pyramidal neurons, that receive excitatory cholinergic input from the medial septal nucleus by acting on 5-HT1A receptors.
Assuntos
Ansiolíticos/farmacologia , Hipocampo/metabolismo , Neurônios/metabolismo , Piperazinas/farmacologia , Pirimidinas/farmacologia , Núcleos da Rafe/fisiologia , Serotonina/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina , Animais , Atropina/farmacologia , Iontoforese , Isoindóis , Masculino , Neurônios/efeitos dos fármacos , Sistema Nervoso Parassimpático/fisiologia , Tratos Piramidais/efeitos dos fármacos , Tratos Piramidais/metabolismo , Ratos , Ratos Endogâmicos , Tetra-Hidronaftalenos/farmacologiaRESUMO
This study was undertaken to elucidate the role of extraocular proprioception in the vestibulo-ocular reflex, using pigmented rabbits. The presence of extraocular afferent projections in the ophthalmic branch (OB) of the trigeminal nerve was confirmed by retrograde transport of horseradish peroxidase. The OB of the left trigeminal nerve was transected at its junction with the trigeminal ganglion. Vestibular nystagmus was produced by rotating the animal clockwise and counter-clockwise in the horizontal plane in a dark room. The number and direction of the quick phase of nystagmus induced by rotation in the eye on the operated side were not different from those in the eye on the unoperated side or from those before the transection. However, the eye on the operated side moved slowly and unstably without directional preponderance during and after rotation at an angular velocity of 30 degrees/sec. In the sham-operated and unoperated groups, when the angular velocity was increased to over 90 degrees/sec, the eyes deviated in the anticompensatory direction to the head movement (the same direction as the head movement) during and immediately after the rotation. At an angular velocity of over 30 degrees/sec, however, the eye on the operated side exhibited anticompensatory response more frequently and markedly than that on the unoperated side. These results suggest that extraocular proprioception is important for fixation of the eye position in spacial relation to the head, and that loss of the sensation readily induces anticompensatory oculomotor response to head movement.
Assuntos
Propriocepção/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Animais , Denervação , Movimentos Oculares , Cabeça , Peroxidase do Rábano Silvestre , Movimento , Nistagmo Fisiológico , Fenômenos Fisiológicos Oculares , Nervo Oftálmico/fisiologia , Coelhos , RotaçãoRESUMO
1. A microiontophoretic study was performed on chloral hydrate-anaesthetized rats to examine the role of D1 receptors in the ventral tegmental area (VTA) neurones, which are inhibited by autoreceptor and D2 receptor agonists. 2. Inhibition by microiontophoretic application of quinpirole (a D2 agonist) of antidromic spikes elicited by stimulation of the nucleus accumbens in dopaminergic neurones of the VTA, was significantly enhanced by simultaneous application of SKF 38393 (D1 agonist), although SKF 38393 alone had little effect on the neurones. 3. In addition, quinpirole-induced inhibition was antagonized by iontophoretic application of domperidone (D2 antagonist), but was not affected by SCH 23390 (D1 antagonist). 4. Furthermore, SKF 38393-induced enhancement of inhibition by quinpirole was antagonized by simultaneous application of SCH 23390. 5. These results suggest that activation of D1 receptors located on the VTA dopaminergic neurones or on non-dopaminergic nerve terminals is not essential for inducing inhibition of the dopaminergic neurones, but enhances D2 receptor-mediated inhibition directly or indirectly via inhibitory neurones.
Assuntos
Dopaminérgicos/farmacologia , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacos , Tegmento Mesencefálico/efeitos dos fármacos , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Benzazepinas/farmacologia , Domperidona/farmacologia , Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Estimulação Elétrica , Ergolinas/farmacologia , Iontoforese , Masculino , Quimpirol , Ratos , Ratos Wistar , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
The relationships between urinary levels of alpha 1-microglobulin (alpha 1M) and ulinastatin (UT) were investigated in C57BL/6J mice, a species which reportedly possesses the gene similar to that of humans for synthesizing the precursor protein of alpha 1M and UT. A positive correlation was established in normal mice. However, repetitive administrations (20 mg/kg, IP, four administrations/12 h) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nullified the positive correlation. A similar phenomenon was induced by ICV-administered MPTP (18 and 36 micrograms) in the animals. Furthermore, L-dopa administration (50 mg/kg, IV) in MPTP-treated (1 week after the final IP administration of MPTP) mice reversed the tendency of MPTP, although the agent alone did not affect the positive correlation in normal mice. These results suggest that nullification of the positive correlation probably was induced by the central effects of MPTP. We have found previously that the lack of a positive correlation between urinary levels of alpha 1M and UT distinguishes Parkinson's disease from other neuropsychiatric diseases such as dementia (Alzheimer-type and vascular dementia), schizophrenia and mood disorders. Our present results displayed a phenomenon that the lack of correlation between urinary levels of alpha 1M and UT in patients with Parkinson's disease is reproducible in MPTP-treated mice.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , alfa-Globulinas/urina , Glicoproteínas/urina , Animais , Antiparkinsonianos/farmacologia , Encéfalo/efeitos dos fármacos , Injeções Intraventriculares , Levodopa/farmacologia , Masculino , Camundongos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/urinaRESUMO
Striatal dopamine contents in C57BL/6J mice were reduced at 24 h after intracerebroventricular (ICV) administration of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) in a dose-dependent manner. A dose of 1.8 microg MPP+ significantly (P < 0.05) suppressed the dopamine contents, whereas a similar dose of MPTP did not. A definite positive correlation between urinary contents of alpha1-microglobulin (alpha1M) and ulinastatin (UT) existed in normal mice. However, this correlation was nullified by ICV administration of 18 and 36 microg MPTP or 1.8 and 18 microg MPP+. With 1.8 microg MPTP, a positive correlation between urinary contents of alpha1M and UT was displayed. The urine volume, creatinine content, glomerular filtration rate, alpha1M and UT contents, and alpha1M/UT ratio of urine collected for 24 h post-ICV administration of MPTP or MPP+, were not statistically different from those of control mice. Our findings suggest that the central effects of MPP+, a neurotoxic metabolite of MPTP, nullify the positive correlation between urinary contents of alpha1M and UT without affecting renal functions.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , 1-Metil-4-fenilpiridínio/farmacologia , alfa-Globulinas/urina , Glicoproteínas/urina , Animais , Dopamina/metabolismo , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neostriado/efeitos dos fármacos , Neostriado/metabolismoRESUMO
Effects of the calmodulin antagonists chlorpromazine, trifluoperazine, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide on phospholipid metabolism were examined in rabbit platelets using [3H]serine, [3H]ethanolamine, [3H]choline, and [3H]glycerol. All these drugs markedly stimulated the incorporation of [3H]serine into phosphatidylserine. On the other hand, these drugs had only a slight effect on the rate of incorporation of [3H]ethanolamine and [3H]choline into the corresponding phospholipid. When [3H]glycerol was used as a precursor of the phospholipids, 3H-labeled phospholipids were mainly composed of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Although the phosphorus content of phosphatidylserine was about 40% of that of phosphatidylcholine in rabbit platelets, the amount of phosphatidylserine labeled with [3H]glycerol was less than 2% of that of the labeled phosphatidylcholine, and calmodulin antagonists slightly stimulated the incorporation of [3H]glycerol into phosphatidylserine. Treatment with calmodulin antagonists caused a marked decrease in the content of endogenous free serine with concomitant increase in the contents of endogenous free ethanolamine and choline. On the other hand, the contents of other free amino acids, including essential and non-essential amino acids, were unchanged. These results suggest that the calmodulin antagonists we used did not affect de novo synthesis of phosphatidylserine, but did stimulate the serine phospholipid base-exchange reaction in rabbit platelets.
Assuntos
Plaquetas/metabolismo , Calmodulina/antagonistas & inibidores , Fosfatidilserinas/sangue , Fosfolipídeos/sangue , Aminoácidos/sangue , Animais , Plaquetas/efeitos dos fármacos , Calmodulina/fisiologia , Clorpromazina/farmacologia , Colina/sangue , Cistina Difosfato/análogos & derivados , Cistina Difosfato/sangue , Etanolamina , Etanolaminas/sangue , Glicerol/sangue , Técnicas In Vitro , Coelhos , Serina/sangue , Trifluoperazina/farmacologia , TrítioRESUMO
Microiontophoretic studies were performed to elucidate the acute effects of methamphetamine on the nucleus accumbens (Acc) neurons receiving input from the parafascicular nucleus (Pf) of the thalamus using rats anesthetized with chloral hydrate. Spike generation upon Pf stimulation was inhibited by conditioning stimuli applied to the ventral tegmental area (VTA), which is rich in dopamine-containing neurons, and by iontophoretic application of methamphetamine as well as dopamine. The VTA-, methamphetamine- and dopamine-induced inhibition of the spikes elicited by Pf stimulation was antagonized during simultaneous application of haloperidol. Glutamate-induced firing was also inhibited during iontophoretic application of methamphetamine and dopamine in neurons receiving input from the Pf, and the inhibition was blocked by simultaneously applied haloperidol. In the reserpine-treated animals, however, the Pf-induced spikes were not affected by methamphetamine, but inhibited by dopamine. These results indicate that methamphetamine inhibits the Acc neurons receiving input from the Pf, probably by releasing dopamine from dopaminergic nerve terminals from the VTA.
Assuntos
Metanfetamina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Dopamina/farmacologia , Glutamatos/farmacologia , Ácido Glutâmico , Haloperidol/farmacologia , Iontoforese , Masculino , Vias Neurais/fisiologia , Núcleo Accumbens/fisiologia , Ratos , Ratos Endogâmicos , Tempo de Reação/efeitos dos fármacos , Reserpina/farmacologia , Tegmento Mesencefálico/fisiologia , Tálamo/fisiologiaRESUMO
Triphasic depressor-pressor-depressor blood pressure responses to neurotensin (NT: 1.67 micrograms/kg i.v.) in anesthetized rats were not elicited when the second dose of NT was administered 20 min after the first injection. Pretreatment of animals with histamine markedly reduced the depressor response to NT, and vice versa. The triphasic blood pressure pattern remained unaffected with acetylcholine and serotonin treatment, and hypotensive effects of acetylcholine and serotonin were not modified by NT. Attenuation of depressor response induced by the second injection of NT was antagonized by pretreatment with prostaglandin synthesis inhibitors such as indomethacin, mefenamic acid and acetylsalicylic acid. These results suggest that histamine and prostaglandins play a role in the development of desensitization to NT in rat blood pressure.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Histamina/farmacologia , Neurotensina/farmacologia , Prostaglandinas/fisiologia , Acetilcolina/farmacologia , Animais , Interações Medicamentosas , Masculino , Ratos , Ratos Endogâmicos , Serotonina/farmacologia , TaquifilaxiaRESUMO
Electrophysiological studies were performed to elucidate the effect of 5-hydroxytryptamine (5-HT) originating in the dorsal raphe nucleus (DR) on neuronal activity in the lateral vestibular nucleus (LVN) neurons, using cats anesthetized with alpha-chloralose. LVN neurons were classified into monosynaptic and polysynaptic neurons according to their responses to vestibular nerve stimulation. Conditioning stimuli applied to the DR inhibited orthodromic spikes elicited by vestibular nerve stimulation predominantly in polysynaptic neurons of the LVN. The iontophoretic application of 5-HT also inhibited orthodromic spikes of the LVN neurons. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretically applied 5-HT in the same neurons. These inhibitions with both treatments were antagonized during the application of methysergide, a 5-HT antagonist. In the majority of LVN polysynaptic neurons that responded to antidromic stimulation of the ipsilateral or contralateral abducens nucleus, orthodromic spikes elicited by vestibular nerve stimulation were inhibited by DR conditioning stimulation and the iontophoretic application of 5-HT. In contrast, LVN neurons that responded to antidromic stimulation of the vestibulospinal tract were rarely affected by these treatments. These results indicate that 5-HT derived from the DR inhibits the synaptic transmission of LVN polysynaptic neurons ascending to the abducens nucleus, and suggest that 5-HT derived from the DR is involved in the regulation of the vestibulo-ocular reflex.
Assuntos
Neurônios/fisiologia , Núcleos da Rafe/fisiologia , Serotonina/fisiologia , Nervo Vestibular/fisiologia , Núcleos Vestibulares/fisiologia , Nervo Abducente/fisiologia , Animais , Gatos , Estimulação Elétrica , Potenciais Evocados , Feminino , Lateralidade Funcional , Iontoforese , Masculino , Metisergida/farmacologia , Neurônios/efeitos dos fármacos , Serotonina/administração & dosagem , Serotonina/farmacologia , Sinapses/fisiologia , Núcleos Vestibulares/efeitos dos fármacosRESUMO
Inhibitory effects of conditioning stimulation of the dorsal raphe nucleus (DR) on the neuron activity in the rostral part of spinal trigeminal nucleus (STN) were studied in cats for the purpose of comparison with the inhibition induced by locus coeruleus (LC) stimulation. DR conditioning stimulation reduced the orthodromic field potential in STN elicited by inferior alveolar nerve stimulation, and enhanced the antidromic field potential in the trigeminal nerve evoked by STN stimulation; but the inhibitory effects of DR stimulation were considerably weaker than those of LC stimulation. In tracking experiments near the raphe nucleus, conditioning stimulation of DR itself produced the most pronounced decrease in the STN field potential. Orthodromic spike number of STN relay neurons was significantly reduced by DR conditioning stimulation; however, the threshold for the conditioning stimulus to the DR was much higher than that to the LC. Antidromic spike generation of the STN neurons was unaltered by conditioning stimulation of both DR and LC. DR stimulation elicited a field potential in STN, which followed high frequency stimuli up to 200 HZ. A single fiber action potential was also obtained in STN by DR stimulation. STN stimulation produced a field potential in DR, which followed high frequency stimuli. It is suggested from these findings that conditioning stimulation of DR produces a direct inhibition of transmission in STN neurons; however, this stimulation has less effect on these neurons than does stimulation of the LC.
Assuntos
Mesencéfalo/fisiologia , Medula Espinal/fisiologia , Nervo Trigêmeo/fisiologia , Animais , Mapeamento Encefálico , Gatos , Ventrículos Cerebrais/fisiologia , Condicionamento Psicológico/fisiologia , Estimulação Elétrica , Potenciais Evocados , Inibição Neural , Vias Neurais , Tempo de ReaçãoRESUMO
Electrophysiological studies using rats were performed to examine the influence of locus coeruleus (LC) on nucleus accumbens (Acc) neurons. Spike generation by hippocampal stimulation was inhibited by both LC conditioning stimulation and iontophoretic application of noradrenaline, but spikes elicited by stimulation of parafascicular nucleus of thalamus were rarely affected by LC conditioning stimulation or noradrenaline. The LC-induced inhibition was antagonized by iontophoretic sotalol, but not by phentolamine, suggesting that noradrenaline derived from the LC inhibits the Acc neurons receiving input from the hippocampus, probably acting on a beta-adrenergic receptor.
Assuntos
Hipocampo/fisiologia , Locus Cerúleo/fisiologia , Núcleo Accumbens/fisiologia , Núcleos Septais/fisiologia , Animais , Estimulação Elétrica , Masculino , Inibição Neural , Vias Neurais/fisiologia , Norepinefrina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos beta/fisiologia , Núcleos Talâmicos/fisiologiaRESUMO
The present study was an attempt to elucidate the role of locus coeruleus (LC) on neuronal activities in the anterior colliculus of rats anesthetized with alpha-chloralose. The spike latency of neurons in the deep grey and white layers of anterior colliculus elicited by stimulation of the optic chiasm (OC), lateral geniculate body (LGB) and visual cortex (VC) was longer than that of neurons in the more superficial layers: optic and intermediate grey layers. When conditioning stimuli were applied to LC, a significant inhibition of spike generation upon OC, LGB and VC stimulation was observed on neurons of deep grey and white layers, but not on those of optic and intermediate grey layers. The conditioning stimulation did not alter spike generation, either in the neurons of deep grey and white layers or those of optic and intermediate grey layers, following stimulation of the superficial grey layer. These results strongly suggest that noradrenaline originating in the LC could produce an inhibition of neuronal activities in the deep grey and white layers, and such is probably the result of inhibition of neurons located in the superficial layer of the anterior colliculus.
Assuntos
Locus Cerúleo/fisiologia , Colículos Superiores/fisiologia , Transmissão Sináptica , Animais , Condicionamento Psicológico/fisiologia , Estimulação Elétrica , Potenciais Evocados , Corpos Geniculados/fisiologia , Interneurônios/fisiologia , Masculino , Inibição Neural , Neurônios/fisiologia , Quiasma Óptico/fisiologia , Ratos , Córtex Visual/fisiologia , Vias Visuais/fisiologiaRESUMO
The role of the ventral tegmental area (VTA), which is rich in dopamine-containing cell bodies, on nucleus accumbens (Acc) neurons was examined. In Acc neurons receiving input from parafascicular nucleus (Pf) of thalamus, VTA conditioning stimulation produced an inhibition of spike generation with Pf stimulation. In contrast, VTA conditioning stimulation did not affect Acc neurons receiving input from limbic structures such as the amygdala nucleus and hippocampus.