RESUMO
Spontaneously hypertensive rats (SHR) are widely used as a model of attention deficit hyperactivity disorder (ADHD) as their ADHD-like behaviors are restored by methylphenidate. However, a postnatal neural development in SHR is unknown. We performed whole cell patch clamp recordings from locus coeruleus (LC) neurons in neonatal [postnatal day (P) 3-5], juvenile (P21-28), and adult (P 49-56) SHR and age-matched Wistar rats to evaluate α1- and α2-adrenergic receptor (ARs) activities at each developmental period. LC neurons in neonatal Wistar rats and SHR showed no difference in resting membrane potential and spontaneous firing rate, while juvenile and adult SHR LC neurons showed depolarized resting membrane potential and faster spontaneous firing rate than in Wistar rats. Blockade of α1-AR activity by prazosin hyperpolarized the membrane and abolished spontaneous firings in all developmental periods in SHR LC neurons, but not in juvenile and adult Wistar rats. α1-AR stimulation by phenylephrine evoked an inward current in juvenile LC neurons in SHR, but not in juvenile Wistar rats. This phenylephrine-induced inward current was abolished by nonselective cation channel blockers. By contrast, α2-AR stimulation-induced outward currents in the presence of an α1-AR antagonist were equivalent in SHR and Wistar LC neurons. These data suggest that Wistar LC neurons lose α1-AR function during development, whereas α1-ARs remain functional in SHR LC neurons. Thus persistent intrinsic activity of α1-ARs may be a neural mechanism contributing to developmental disorders in juvenile SHRs.
Assuntos
Potenciais de Ação , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Locus Cerúleo/fisiologia , Receptores Adrenérgicos alfa 1/metabolismo , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Fatores Etários , Animais , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Locus Cerúleo/citologia , Locus Cerúleo/crescimento & desenvolvimento , Locus Cerúleo/metabolismo , Potenciais da Membrana , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Fenilefrina/farmacologia , Prazosina/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
We investigated the effects of traumatic brain injury (TBI) on the glutamatergic synaptic transmission in the hippocampal CA1 area. A moderate impact (3.8-4.8atm) was applied onto the left parietal cerebral cortex by a fluid percussion injury (FPI) device. Conventional intracellular recordings were made from hippocampal CA1 pyramidal neurons in vitro. Electrophysiological properties of these neurons were compared between three groups (control, FPI-ipsilateral, and FPI-contralateral). The excitability of postsynaptic membrane of CA1 pyramidal neurons was not altered by the moderate FPI; however, the evoked glutamatergic excitatory synaptic transmission in the pyramidal neurons of post-FPI-CA1 was enhanced. Paired-pulse facilitation (PPF) was significantly suppressed in both the FPI-ipsilateral and FPI-contralateral groups and the frequencies of mEPSPs in neurons from the bilateral FPI groups were greater than the frequency in the control group. These results suggest that the glutamatergic synaptic transmission in the hipppocampal CA1 area is facilitated through presynaptic mechanisms after TBI.
Assuntos
Lesões Encefálicas/metabolismo , Epilepsia/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Terminações Pré-Sinápticas/metabolismo , Transmissão Sináptica/fisiologia , Potenciais de Ação/fisiologia , Animais , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Modelos Animais de Doenças , Epilepsia/etiologia , Epilepsia/fisiopatologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/fisiopatologia , Masculino , Plasticidade Neuronal/fisiologia , Células Piramidais/metabolismo , Ratos , Ratos WistarRESUMO
Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABA(A) and GABA(B) receptor antagonists. Bath application of 5-HT (10 microm) for 5-10 min increased the amplitude of the EPSP and EPSC. (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC. Alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 microm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 microm), selective 5-HT2B and 5-HT2C receptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 microm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10 microm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by alpha-methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 microm) and alpha-methyl-5-HT (10 microm) increased the frequency of miniature EPSPs (mEPSPs) without changing the mEPSP amplitude. The ratio of the paired pulse facilitation was significantly decreased by 5-HT and alpha-methyl-5-HT. The 5-HT-induced facilitation of the EPSP was blocked by calphostin C (100 nm), a specific protein kinase C (PKC) inhibitor, but not by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 microm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 microm) mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT2A receptors that link with PKC in rat DLSN neurons.
Assuntos
Terminações Pré-Sinápticas/metabolismo , Proteína Quinase C/metabolismo , Receptores de Serotonina/metabolismo , Núcleos Septais/metabolismo , Transmissão Sináptica/fisiologia , Animais , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Antagonistas GABAérgicos/farmacologia , Antagonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-B , Proteínas de Ligação ao GTP/efeitos dos fármacos , Proteínas de Ligação ao GTP/metabolismo , Ácido Glutâmico/farmacologia , Técnicas In Vitro , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteína Quinase C/antagonistas & inibidores , Ratos , Ratos Wistar , Receptor 5-HT2A de Serotonina , Núcleos Septais/citologia , Núcleos Septais/efeitos dos fármacos , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Fatores de Virulência de Bordetella/farmacologiaRESUMO
OBJECTIVES: We sought to assess whether mechanical unloading has beneficial effects on cardiomyocytes from doxorubicin-induced cardiomyopathy in rats. BACKGROUND: Mechanical unloading by a left ventricular assist device (LVAD) improves the cardiac function of terminal heart failure in humans. However, previous animal studies have failed to demonstrate beneficial effects of mechanical unloading in the myocardium. METHODS: The effects of mechanical unloading by heterotopic abdominal heart transplantation were evaluated in the myocardium from doxorubicin-treated rats by analyzing the intracellular free calcium level ([Ca(2+)](i)) and the levels of intracellular Ca(2+)-regulatory proteins. RESULTS: In doxorubicin-treated rats, the duration of cell shortening and [Ca(2+)](i) transients in cardiomyocytes was prolonged (432 +/- 28.2% of control in 50% relaxation time; 184 +/- 10.5% of control in [Ca(2+)](i) 50% decay time). Such prolonged time courses significantly recovered after mechanical unloading (114 +/- 10.4% of control in 50% relaxation time; 114 +/- 5.8% of control in 50% decay time). These effects were accompanied by an increase in sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) protein levels (0.97 +/- 0.05 in unloaded hearts vs. 0.41+/- 0.09 in non-unloaded hearts). The levels of other intracellular Ca(2+)-regulatory proteins (phospholamban and ryanodine receptor) were not altered after mechanical unloading in doxorubicin-treated hearts. These parameters in unloaded hearts without doxorubicin treatment were similar to normal hearts. CONCLUSIONS: Mechanical unloading increases functional sarcoplasmic reticulum Ca(2+) ATPase and improves [Ca(2+)](i) handling and contractility in rats with doxorubicin-induced cardiomyopathy. These beneficial effects of mechanical unloading were not observed in normal hearts.
Assuntos
Cálcio/fisiologia , Cardiomiopatias/fisiopatologia , Transplante de Coração/fisiologia , Contração Miocárdica/fisiologia , Miócitos Cardíacos/fisiologia , Animais , Antibióticos Antineoplásicos , ATPases Transportadoras de Cálcio/fisiologia , Cardiomiopatias/induzido quimicamente , Doxorrubicina , Miocárdio/ultraestrutura , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canal de Liberação de Cálcio do Receptor de Rianodina/fisiologia , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo SarcoplasmáticoRESUMO
Rhubarb extracts provide neuroprotection after brain injury, but the mechanism of this protective effect is not known. The present study tests the hypothesis that rhubarb extracts interfere with the release of glutamate by brain neurons and, therefore, reduce glutamate excitotoxicity. To this end, the effects of emodin, an anthraquinone derivative extracted from Rheum tanguticum Maxim. Ex. Balf, on the synaptic transmission of CA1 pyramidal neurons in rat hippocampus were studied in vitro. The excitatory postsynaptic potential (EPSP) was depressed by bath-application of emodin (0.3-30 microM). Paired-pulse facilitation (PPF) of the EPSP was significantly increased by emodin. The monosynaptic inhibitory postsynaptic potential (IPSP) recorded in the presence of glutamate receptor antagonists (DNQX and AP5) was not altered by emodin. Emodin decreased the frequency, but not the amplitude, of the miniature EPSP (mEPSP). The inhibition of the EPSP induced by emodin was blocked by either 8-CPT, an adenosine A1 receptor antagonist, or by adenosine deaminase. These results suggest that emodin inhibits the EPSP by decreasing the release of glutamate from Schaffer collateral/commissural terminals via the activation of adenosine A1 receptors in rat hippocampal CA1 area and that the neuroprotective effects of rhubarb extracts may result from decreased glutamate excitotoxicity.
Assuntos
Emodina/farmacologia , Hipocampo/citologia , Células Piramidais/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Adenosina/farmacologia , Adenosina Desaminase/farmacologia , Animais , Bicuculina/análogos & derivados , Bicuculina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletrofisiologia/métodos , Inibidores Enzimáticos/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Técnicas In Vitro , Masculino , Inibição Neural/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1 , Células Piramidais/fisiologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Transmissão Sináptica/fisiologia , Teofilina/análogos & derivados , Teofilina/farmacologia , Valina/análogos & derivados , Valina/farmacologiaRESUMO
BACKGROUND: 5-dihydroxyanthraquinone-2-carboxylic acid (rhein) inhibits oxidoreduction induced by reducing nicotingamide adenine dinucleotide in the mitochondria and reducing reactive oxygen species, it also suppresses lipid peroxidation in rat brain homogenates. This study was to assess the effects of anthraquinone derivatives, rhein on synaptic transmission in the rat hippocampal CA1 pyramidal cell layer by intracellular recording. METHODS: The excitatory postsynaptic potential (EPSP) evoked by stimulation of the Schaffer collaterals in the presence of bicuculline (15 micromol/L) was depressed by application of rhein (0.3 - 30 micromol/L). The amplitude of the EPSP was restored within 20 minutes after removal of rhein from the supernatant. At a concentration of 30 micromol/L, rhein reduced the amplitude of the EPSP to 42% +/- 3.7% (n = 24) of the control. Subsequently, wavelet spectral entropy was used to analyze the EPSP. RESULTS: A strong positive correlation was observed between the wavelet spectral entropy and other parameters such as amplitude, slope of rising phase and slope of descending phase of the EPSP. The paired-pulse facilitation (PPF) of the EPSP was significantly increased by rhein (30 micromol/L). The inhibitory postsynaptic potential (IPSP) recorded in the presence of CNQX (20 micromol/L) and APV (40 micromol/L) is not altered by rhein (30 micromol/L). CONCLUSIONS: Rhein (30 micromol/L) can decrease the frequency but not the amplitude of the miniature EPSP (mEPSP). It is suggested that rhein inhibits excitatory synaptic transmission by decreasing the release of glutamate in rat hippocampal CA1 pyramidal neurons.
Assuntos
Antraquinonas/farmacologia , Entropia , Hipocampo/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Antraquinonas/química , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Hipocampo/fisiologia , Técnicas In Vitro , Masculino , Ratos , Ratos WistarRESUMO
Effects of milnacipran (MIL), a selective serotonin and noradrenaline (NA) reuptake inhibitor, on the neuronal excitability and synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular and whole-cell patch-clamp recording techniques. We compared MIL and methylphenidate (MPH), a selective NA and dopamine reuptake inhibitor, as a therapeutic agent for attention deficit/hyperactivity disorder. Application of MPH (1-100 microM) and MIL (1-100 microM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response in LC neurons in a concentration-dependent manner. Spontaneous firing of LC neurons was blocked during the hyperpolarization. The MIL-induced hyperpolarization was blocked by yohimbine (1 microM), an antagonist for alpha-adrenoceptors. These results suggest that the MIL-induced hyperpolarization is mediated by NA via alpha2-adrenoceptors in LC neurons. Under the whole-cell patch-clamp condition, prolonged application of MIL produced an outward current which lasted as long as MIL existed in the ACSF. The outward current induced by NA was enhanced by MIL in LC neurons. MIL enhanced the amplitude and duration of the inhibitory postsynaptic potential, while it depressed the excitatory postsynaptic potential. The results indicated that both MIL and MPH showed almost the same effects on neuronal activity and synaptic transmission in the rat LC. These results suggest that MIL increases the concentration of NA at synaptic clefts by inhibiting the NA reuptake system in the rat LC.
Assuntos
Ciclopropanos/farmacologia , Locus Cerúleo/efeitos dos fármacos , Neurônios/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Locus Cerúleo/citologia , Masculino , Metilfenidato/farmacologia , Milnaciprano , Neurônios/efeitos dos fármacos , Norepinefrina/metabolismo , Norepinefrina/farmacologia , Técnicas de Patch-Clamp , Ratos , Ratos WistarRESUMO
Effects of 5-hydroxytryptamine (5-HT) on inhibitory synaptic transmission in the rat dorsolateral septal nucleus (DLSN) were examined by conventional intracellular and voltage-clamp recording methods. 5-HT (1-30 microM) depressed the monosynaptic fast IPSC evoked by local stimulation of the DLSN in the presence of DNQX, AP5 and CGP 55845A. CP 93129, a selective 5-HT1B receptor agonist, depressed the fast IPSC. The 5-HT-induced depression of the fast IPSC was attenuated by SB 216641, a selective antagonist for 5-HT1B receptors. 5-HT did not change the inward currents mediated by GABAA receptors, suggesting that 5-HT presynaptically inhibited the fast IPSC. 5-HT and CP 93129 depressed the frequency of miniature fast IPSPs (mIPSPs) without changing their amplitudes. Neither a selective protein kinase A inhibitor, H-89, nor a selective protein kinase C inhibitor, calphostin C, blocked the 5-HT-induced depression of the fast IPSC. N-Ethylmaleimide (NEM) blocked the 5-HT-induced depression of the evoked IPSC. These results suggest that activation of presynaptic 5-HT1B receptors depresses the release of GABA via a pertussis toxin (PTX)-sensitive G-protein in the rat DLSN.
Assuntos
Inibição Neural/fisiologia , Neurônios/fisiologia , Terminações Pré-Sinápticas/fisiologia , Receptor 5-HT1B de Serotonina/fisiologia , Núcleos Septais/citologia , Análise de Variância , Animais , Benzamidas/farmacologia , Compostos de Bifenilo/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Técnicas In Vitro , Masculino , Potenciais da Membrana/fisiologia , Muscimol/farmacologia , Oxidiazóis/farmacologia , Técnicas de Patch-Clamp/métodos , Toxina Pertussis/farmacologia , Ácidos Fosfínicos/farmacologia , Piperazinas/farmacologia , Propanolaminas/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Transmissão Sináptica , Ácido gama-Aminobutírico/farmacologia , ômega-Agatoxina IVA/farmacologia , ômega-Conotoxina GVIA/farmacologiaRESUMO
Effects of temperature increase on the neuronal activity of hippocampal CA2-CA1 regions were examined by using optical and electrophysiological recording techniques. Stimulation of the Schaffer collaterals at the CA2 region evoked depolarizing optical signals that spread toward the CA1 region at 32 degrees C. The optical signal recorded by 49 pixels was characterized by fast and slow components that were closely related to presynaptic action potentials and excitatory postsynaptic responses, respectively. The optical signal was depressed by temperature increase to 38-40 degrees C. The temperature increase to 38 degrees C produced a hyperpolarization and a depression of the excitatory postsynaptic potential (EPSP) in single hippocampal CA1 pyramidal neurons. The depression of the neuronal activity induced by temperature increase was attenuated by application of glucose (22 mM) or pyruvate (22 mM). Adenosine (200 microM) did not block the presynaptic action potential but strongly depressed the excitatory postsynaptic response. 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (10 microM), an antagonist for adenosine A(1) receptors, attenuated the depression of the excitatory postsynaptic response but not the inhibition of the presynaptic action potential at 38 degrees C. These results suggest that adenosine mediates the high-temperature-induced depression of the excitatory synaptic transmission but not that of action potential propagation in rat CA1 neurons.
Assuntos
Potenciais de Ação/fisiologia , Hipocampo/fisiologia , Temperatura Alta , Neurônios/fisiologia , Terminações Pré-Sinápticas/fisiologia , Temperatura , Potenciais de Ação/efeitos dos fármacos , Adenosina/fisiologia , Animais , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Neurônios/efeitos dos fármacos , Terminações Pré-Sinápticas/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Using optical recording techniques, we examined whether nitric oxide (NO) is implicated in the impairment of the activity of hippocampal CA1 neurons induced by mild heat stress. A temperature increase from 32 to 38 degrees C reversibly depressed the neuronal activity in hippocampal slices. L-Arginine (1 mM), an NO donor, enhanced the heat-induced depression of the activity of hippocampal CA1 neurons. N(omega)-Nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, attenuated the inhibition of the neuronal activity induced by a temperature increase. Methylcobalamin (10 microM), a vitamin B(12) analogue that reduces NO production, reduced the heat-induced depression of the neuronal activity. These results suggest that NO contributes, at least in part, to the heat-induced depression of the neuronal activity in the hippocampal CA1 region.
Assuntos
Hipocampo/fisiologia , Neurônios/fisiologia , Óxido Nítrico/fisiologia , Vitamina B 12/análogos & derivados , Animais , Arginina/farmacologia , Estimulação Elétrica , Eletrofisiologia , Calefação , Hipocampo/citologia , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/antagonistas & inibidores , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óptica e Fotônica , Ratos , Ratos Wistar , Temperatura , Vitamina B 12/farmacologiaRESUMO
Effects of fluid percussion injury (FPI) of the parietal cerebral cortex on the neuronal activity in the temporal region of the rat hippocampal CA1 area were investigated by using optical and extracellular recording techniques. Application of moderate impact (1.5-2.0 atm) to the parietal cerebral cortex enhanced the optical signal of the neuronal activity in the ipsilateral hippocampal CA1 area. The field potential evoked by the Schaffer collaterals had multiple population spikes in the ipsilateral hippocampal CA1 pyramidal cell layer. Bicuculline (15 microM) increased the amplitude and the number of population spikes of the field potential even after the brain injury. These results suggest that FPI produces hyperexcitability of hippocampal CA1 neurons, probably by increasing the activity of the Schaffer collaterals of hippocampal CA3 neurons.
Assuntos
Lesões Encefálicas/fisiopatologia , Córtex Cerebral/lesões , Hipocampo/citologia , Neurônios/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Bicuculina/farmacologia , Antagonistas GABAérgicos/farmacologia , Hipocampo/fisiopatologia , Masculino , Transtornos da Memória/fisiopatologia , Ratos , Ratos WistarRESUMO
Effects of L-arginine on the heat-induced depression of the neuronal activity in the hippocampal CA1 area were investigated using optical recording techniques. An increase in the temperature of hippocampal neurons from 32 degrees C to 38 degrees C reversibly depressed the fast and slow components of the optical response to stimulation of the Schaffer collaterals that correspond to the presynaptic action potential and excitatory postsynaptic response, respectively. The neuronal activity recovered almost completely after cooling the hippocampal neurons back to 32 degrees C. A temperature increase to 40 degrees C produced irreversible depression of the neuronal activity. Pyruvate, but not lactate, in the artificial cerebrospinal fluid (ACSF) attenuated the depression of the neuronal activity induced by a temperature increase to 38 degrees C. Bath-application of L-arginine (1 mM), a nitric oxide (NO) donor, enhanced the depression of the neuronal activity at 38 degrees C. In the presence of L-arginine, the recovery of neuronal activity, upon return to 32 degrees C, was incomplete. The contribution of NO to the heat-induced impairment of the neuronal activity was discussed.
Assuntos
Arginina/farmacologia , Hipocampo/efeitos dos fármacos , Temperatura Alta , Neurônios/efeitos dos fármacos , Animais , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Neurônios/metabolismo , Neurônios/fisiologia , Óxido Nítrico/biossíntese , Ratos , Ratos WistarRESUMO
Effects of methylphenidate (MPH), an agent used clinically for the treatment of children presenting the attention-deficit/hyperactivity disorder (AD/HD), on synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular recording methods. Bath-application of MPH (30 nM-3 microM) increased the amplitude of the inhibitory postsynaptic potential (IPSP), while it did not change the amplitude of the excitatory postsynaptic potential (EPSP). MPH increased the time-to-peak and the half-decay time of the IPSP in LC neurons. MPH increased the amplitude of spontaneous IPSP: individual spontaneous IPSPs merged one into the other so as to produce regular, long-lasting waves of hyperpolarization. Clonidine (10 nM), a selective agonist for alpha 2-adrenoceptors, depressed the IPSP without affecting the EPSP in LC neurons. The results suggest that MPH enhances inhibitory synaptic transmission in the rat LC by depressing the norepinephrine (NE) re-uptake system.
Assuntos
Locus Cerúleo/efeitos dos fármacos , Metilfenidato/farmacologia , Animais , Clonidina/farmacologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Humanos , Técnicas In Vitro , Locus Cerúleo/fisiologia , Masculino , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacosRESUMO
Effects of milnacipran (MIL), a serotonin and noradrenaline reuptake inhibitor (SNRI), on synaptic transmission were examined in the rat locus coeruleus (LC). Bath-application of MIL produced a hyperpolarization associated with a decrease in input resistance of LC neurons. The MIL-induced hyperpolarization reversed polarity near the equilibrium potential of K+. The MIL-induced hyperpolarization was blocked by yohimbine (1 microM). Clonidine, but not serotonin (5-hydroxytryptamine; 5-HT), produced a hyperpolarizing potential in LC neurons. The MIL-induced hyperpolarization reversed polarity at -114 +/- 3 mV (n=4). MIL (0.1-10 microM) depressed the amplitude of the excitatory postsynaptic potential (EPSP), while it enhanced the amplitude and duration of the inhibitory postsynaptic potential (IPSP). These results suggest that MIL hyperpolarizes LC neurons and enhances the IPSP by increasing endogenous noradrenaline (NA) concentration at synapses in LC neurons.
Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Ciclopropanos/farmacologia , Locus Cerúleo/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Locus Cerúleo/fisiologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Milnaciprano , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
Effects of edaravone, a free radical scavenger, on post-traumatic impairment of long-term potentiation (LTP) were examined in granule cell layers of the dentate gyrus (DG) in vitro. Field EPSPs (fEPSPs) evoked by stimulation of the perforant path (PP) were recorded extracellularly in the DG one week after a moderate impact applied by a fluid percussion injury (FPI) device. High frequency stimulation (HFS) of the PP caused LTP of the fEPSP-slope in slices from naïve and sham-operated rats, however, the LTP was strongly depressed in slices from FPI rats. Intraperitoneal administration of edaravone 15 min after FPI prevented the hyperactivities of DG neurons and attenuated impairment of the LTP in FPI rat dentate granular cells. In vitro application of spermine NONOate (sp-NO), a nitric oxide (NO) donor, for 30 min produced a gradual increase in the fEPSP-slope, lasting for more than 2 h. Edaravone attenuated the enhancement of the fEPSP-slope induced by sp-NO. After sp-NO treatment HFS could not produce an obvious LTP in the DG granule cell layer. Pretreatment of DG slices with edaravone prevented the sp-NO-induced impairment of LTP. These results suggest that administration of edaravone after FPI protects against post-traumatic impairment of LTP in granule cell layers of the DG, possibly by scavenging NO-related radicals.
Assuntos
Antipirina/análogos & derivados , Lesões Encefálicas/fisiopatologia , Giro Denteado/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Animais , Antipirina/administração & dosagem , Antipirina/farmacologia , Lesões Encefálicas/patologia , Giro Denteado/patologia , Giro Denteado/fisiologia , Edaravone , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Sequestradores de Radicais Livres/administração & dosagem , Injeções Intraperitoneais , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Modelos Animais , Plasticidade Neuronal/fisiologia , Doadores de Óxido Nítrico/farmacologia , Ratos , Ratos Wistar , Espermina/análogos & derivados , Espermina/farmacologia , Sinapses/fisiologiaAssuntos
Dopamina/farmacologia , Núcleos Septais/efeitos dos fármacos , Animais , Masculino , Potenciais da Membrana/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Ratos , Ratos Wistar , Núcleos Septais/fisiologia , Transmissão Sináptica/efeitos dos fármacosRESUMO
The present study examined the effect of methylphenidate (MPH), a psychostimulant, on nor-adrenergic transmission in the locus coeruleus (LC) of juvenile rats. Intracellular recordings showed that MPH (>3 µM) produced a hyperpolarizing response associated with a decrease in the rate of spontaneously firing action potentials. MPH (1 µM) enhanced the amplitude of the inhibitory postsynaptic potential (IPSP) mediated by norepinephrine (NE), but did not change the excitatory postsynaptic potential (EPSP) mediated by excitatory amino acids. Whole-cell patch-clamp recordings showed that MPH (0.3-30 µM) produced an outward current (I(MPH)) and enhanced the inhibitory postsynaptic current (IPSC) in neurons of the juvenile rat LC. MPH (30 µM) enhanced the NE-induced outward current (I(NE)). Bath-application of yohimbine (1 µM) produced an inward current and blocked the MPH-induced enhancement of the IPSC. Yohimbine (1 µM) depressed not only the I(NE) but also the I(MPH) in juvenile rat LC neurons. The current-voltage relationship of the I(MPH) showed inward rectification and reversed polarity at -91.1±4.3 mV (n=5). Ba(2+) (100 µM) blocked the I(MPH), indicating that the I(MPH) is mediated by Ba(2+)-sensitive inward rectifier K(+) current. These results suggest that MPH enhances inhibitory synaptic transmission by increasing the concentration of NE at noradrenergic synapses in juvenile rat LC neurons.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Locus Cerúleo/metabolismo , Metilfenidato/farmacologia , Norepinefrina/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores , Técnicas In Vitro , Locus Cerúleo/fisiologia , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Endogâmicos WKYRESUMO
The present experiment examined the effect of mild hypothermia (35 degrees C) on the post-traumatic hyperactivity of rat hippocampal CA1 neurons in horizontal brain slices. One week after fluid percussion injury (FPI), the optical response evoked by stimulation of the Schaffer collaterals increased in amplitude and propagation area in hippocampal CA1 slices. FPI did not alter the fast optical response that reflected the action potential of the Schaffer collaterals but enhanced the slow component that reflected the excitatory postsynaptic response. FPI increased the slope of the input-output relation (I/O function), suggesting that FPI increases the efficacy of excitatory synaptic transmission in the hippocampal CA1 pyramidal neurons. To examine the effect of low temperature on post-traumatic hyperactivity of hippocampal CA1 neurons, mild hypothermia (35 degrees C) was administered to rats 15 min after FPI and maintained for 1-3 h. One week after FPI, the activity of hippocampal CA1 neurons in rats with mild hypothermia appeared to be reduced as compared with those receiving FPI alone. The post-traumatic enhancement of the I/O function of the slow optical response was prevented by mild hypothermia. These results suggest that mild hypothermia applied 15 min after FPI attenuates the post-traumatic hyperactivity of excitatory synapses in rat hippocampal CA1 neurons.
Assuntos
Lesões Encefálicas/fisiopatologia , Região CA1 Hipocampal/fisiopatologia , Hipotermia Induzida , Transmissão Sináptica , Animais , Cálcio/metabolismo , Potenciais Pós-Sinápticos Excitadores , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
The neurochemical phenotypes of the transient receptor potential melastatin-8 (TRPM8)-immunoreactive afferent neurons innervating the rat urinary bladder were examined by using a highly sensitive tyramide signal amplification method, combined with wheat-germ agglutinin-horseradish peroxidase (WGA-HRP) retrograde tracing. TRPM8-immunoreactivity was detected in a small proportion of the WGA-HRP-labeled bladder afferent neurons in the dorsal root ganglia of the Th13-L1 (1.14%) and the L6-S1 (1.27%), and these neurons were small in size (<600 microm(2)). The 82.6+/-3.8% of the TRPM8-immunoreactive bladder afferent neurons and 80.9+/-1.5% of the total population of the TRPM8-immunoreactive afferent neurons in the observed dorsal root ganglia expressed NF200. On the other hand, the proportions of the co-expression of TRPM8 and nociceptive markers such as calcitonin gene-related peptide (CGRP), transient receptor potential vanilloid-1 (TRPV1), and isolectin B4 (IB4) in the bladder afferent neurons (81.5+/-5.2% for CGRP, 36.1+/-4.0% for TRPV1, and 15.8+/-5.5% for IB4) were higher in comparison to those in the total population of the TRPM8-immunoreactive afferent neurons (21.9+/-2.4% for CGRP, 16.6+/-1.7% for TRPV1, and 5.4+/-0.5% for IB4), although no significant difference existed for IB4. Our results suggest that the TRPM8-expressing bladder afferents should be classified as Adelta-fibers and C-fibers, while some of these afferents may be involved in nociceptive sensations.
Assuntos
Gânglios Espinais/metabolismo , Nociceptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPM/metabolismo , Bexiga Urinária/inervação , Fibras Aferentes Viscerais/metabolismo , Animais , Biomarcadores/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Contagem de Células , Feminino , Gânglios Espinais/citologia , Imuno-Histoquímica , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/ultraestrutura , Fibras Nervosas Amielínicas/metabolismo , Fibras Nervosas Amielínicas/ultraestrutura , Técnicas de Rastreamento Neuroanatômico/métodos , Proteínas de Neurofilamentos/metabolismo , Nociceptores/citologia , Dor/metabolismo , Dor/fisiopatologia , Lectinas de Plantas , Ratos , Ratos Wistar , Células Receptoras Sensoriais/citologia , Canais de Cátion TRPV/metabolismo , Fibras Aferentes Viscerais/citologia , Conjugado Aglutinina do Germe de Trigo-Peroxidase do Rábano SilvestreRESUMO
The lateral septal nucleus receives a diffuse dopaminergic input originating from the ventral tegmental area of the brain stem. We examined whether dopamine (DA) modulates synaptic transmission in the slice preparation of the rat dorsolateral septal nucleus (DLSN). Bath application (10-15 min) of DA (30 muM) markedly depressed the amplitude of fast and slow inhibitory postsynaptic potentials (IPSPs) in DLSN neurons, while it produced only a minor depression of the amplitude of excitatory postsynaptic potentials (EPSPs) obtained in the presence of bicuculline. DA (30 muM) depressed the monosynaptic fast IPSP to approximately 50% of control, but did not depress the inward current (I(GABA)) induced by exogenous gamma-aminobutyric acid (GABA). DA decreased the frequency of miniature fast IPSPs (m-fIPSPs) without significantly changing their amplitude. PD 168077, a selective D4 receptor agonist, depressed the fast and slow IPSPs but not the EPSP and decreased the frequency of m-fIPSPs. Both DA and PD 168077 increased the paired-pulse ratio of the monosynaptic fast IPSP. The inhibitory effect of DA on the fast IPSP was significantly attenuated by L-741,742, an antagonist at D4 receptors, but not by SCH 23390 and sulpiride, a D1-like and a D2-like receptor antagonist, respectively. N-ethylmaleimide, a blocker of pertussis toxin (PTX)-sensitive G protein (G(i/o)), attenuated the DA-induced depression of the fast IPSP. N-[2-((p-bromocinnamyl) amino)ethyl]-5-isoquinoline sulfonamide, a protein kinase A (PKA) inhibitor, attenuated the DA-induced depression of the fast IPSP. These results suggest that DA inhibits spontaneous and evoked release of GABA via the D4 receptor-G(i)-protein-PKA system in DLSN neurons.