RESUMO
Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator reference compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions, SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.
RESUMO
BACKGROUND: Magnetic field therapy is a popular approach to pain therapy, but scientific evidence on treatment effects or even effects on sensory and pain perception in healthy controls is scarce. METHODS: In the present randomized, placebo-controlled study, we investigated the influence of static magnetic field exposure on sensory (touch) and pain (pinprick, pressure and heat) perception. Eighteen healthy volunteers (age: 23 ± 2 years, nine women) underwent three 10-min static magnetic field exposures using field strengths of 0 T (placebo), 1.5 T and 3 T within clinical MR scanners in randomized order on three separate days. Participants were blinded to magnetic field strength. Experimental sensory and pain testing was performed immediately before and after each magnetic field exposure. RESULTS: There was no significant effect of field strength on the assessed experimental sensory and pain testing parameters (mechanical detection threshold, pinprick threshold, pressure pain threshold, heat pain threshold and suprathreshold heat pain rating). CONCLUSION: We found no evidence that a 10-min 1.5 T or 3 T static magnetic field exposure affects experimental sensory or pain perception in young healthy volunteers. SIGNIFICANCE: We used clinical MR scanners to investigate the effect of magnetic fields on pain perception. Using a rigorous, straightforward, placebo-controlled design, no effect of static magnetic fields on human experimental pain perception was detected. This provides a base for a more systematic investigation of magnetic field effects on pain.
Assuntos
Magnetoterapia , Percepção da Dor , Limiar da Dor , Percepção do Tato , Adulto , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Temperatura Alta , Humanos , Masculino , Medição da Dor , Adulto JovemRESUMO
Pharmacological and functional data suggest the existence of uridine (Urd) receptors in the central nervous system (CNS). In the present study, simultaneous extracellular single unit recording and microiontophoretic injection of the pyrimidine nucleoside Urd was used to provide evidence for the presence of Urd-sensitive neurons in the thalamus and the cerebral cortex of Long Evans rats. Twenty-two neurons in the thalamus (24% of recorded neurons) and 17 neurons in the cortex (55%) responded to the direct iontophoresis of Urd. The majority of Urd-sensitive neurons in the thalamus and cortex (82% and 59%, respectively) increased their firing rate in response to Urd. In contrary, adenosine (Ado) and uridine 5'-triphosphate (UTP) decreased the firing rate of all responding neurons in the thalamus, and the majority of responding neurons in the cortex (83% and 87%, respectively). Functional relevance of Urd-sensitive neurons was investigated in spontaneously epileptic freely moving Long Evans and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Intraperitoneal (i.p.) injection of 500mg/kg Urd decreased epileptic activity (210-270min after injection) in both rat strains. Intraperitoneal administration of 1000mg/kg Urd decreased the number of spike-wave discharges (SWDs) between 150-270min and 90-270min in Long Evans and WAG/Rij rats, respectively. The effect of Urd was long-lasting in both rat strains as the higher dose significantly decreased the number of SWDs even 24h after Urd injection. The present results suggest that Urd-sensitive neurons in the thalamus and the cerebral cortex may play a role in the antiepileptic action of Urd possibly via modulation of thalamocortical neuronal circuits.
Assuntos
Anticonvulsivantes/farmacologia , Inibição Neural , Neurônios/efeitos dos fármacos , Uridina/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiologia , Epilepsia Tipo Ausência/fisiopatologia , Masculino , Neurônios/fisiologia , Ratos , Ratos Long-Evans , Ratos Wistar , Tálamo/efeitos dos fármacos , Tálamo/fisiologiaRESUMO
In the present experiment, the effect of a single 30 min inhomogeneous static magnetic field (SMF) exposure on thermal pain threshold (TPT) was examined in 15 young healthy human volunteers. The SMF had a maximum peak-to-peak amplitude of 330 mT with a maximum gradient of 13.2 T/m. In either of two experimental sessions (SMF or SHAM), four blocks of 12 TPT trials were carried out under SMF or SHAM exposure on all fingertips of the dominant hand, excluding the thumb. TPT and visual analog scale (VAS) data were recorded at 0, 15, and 30 min exposure time, and 30 min following exposure. SMF treatment resulted in a statistically significant increase in TPT during the entire exposure duration and diminished within-block thermal habituation, leaving pain perception unchanged. These results indicate that SMF-induced peripheral neuronal or circulatory mechanisms may be involved in the observed TPT increase by setting the pain fibre adaptation potential to higher levels.
Assuntos
Saúde , Magnetoterapia/métodos , Limiar da Dor , Temperatura , Adolescente , Adulto , Feminino , Humanos , Hiperalgesia/terapia , Masculino , Adulto JovemRESUMO
The more we anticipate a response to a predictable stimulus, the faster we react. This empirical observation has been confirmed and quantified by many investigators suggesting that the processing of behaviorally relevant stimuli is facilitated by probability-based confidence of anticipation. However, the exact neural mechanisms underlying this phenomenon are largely unknown. Here we show that performance changes related to different levels of expectancy originate in dynamic modulation of delta oscillation phase. Our results obtained in rhythmic auditory target detection tasks indicated significant entrainment of the EEG delta rhythm to the onset of the target tones with increasing phase synchronization at higher levels of predictability. Reaction times correlated with the phase of the delta band oscillation at target onset. The fastest reactions occurred during the delta phase that most commonly coincided with the target event in the high expectancy conditions. These results suggest that low-frequency oscillations play a functional role in human anticipatory mechanisms, presumably by modulating synchronized rhythmic fluctuations in the excitability of large neuronal populations and by facilitating efficient task-related neuronal communication among brain areas responsible for sensory processing and response execution.
Assuntos
Atenção/fisiologia , Relógios Biológicos/fisiologia , Córtex Cerebral/fisiologia , Tempo de Reação/fisiologia , Estimulação Acústica , Adulto , Análise de Variância , Sinais (Psicologia) , Eletroencefalografia , Potenciais Evocados/fisiologia , Humanos , Processamento de Sinais Assistido por ComputadorRESUMO
Although mast cells are immune cells of hematopoietic origin, they can be found in parts of the central nervous system of many mammalian species. In the rat brain they are located in the thalamic region. Their function is not defined yet, although they are mostly known to secrete several chemicals, which may influence the surrounding neurons. There are no in vivo electrophysiological data available on the possible effects of brain mast cells on neurons. In this study, we used a combined method of microiontophoresis and extracellular single unit recording to simultaneously activate mast cells and record neuronal action potentials. Four-barrelled micropipettes were used for recording neuronal activity and for microiontophoretic application of mast cell degranulator Compound 48/80 (C48/80). Spike sorting routines were performed on-line and off-line to ensure that data were always recorded from a single neuron. C48/80 did not modify the firing rate of cortical neurons (no mast cells are found there), however, it caused excitation (n = 16/37, 43%), or inhibition (n = 9/37, 24%) in thalamic neurons possibly due to mast cell activation. Further investigations will clarify the biochemical nature of changes in neural excitability due to mast cell degranulation in the mammalian brain.
Assuntos
Encéfalo/citologia , Iontoforese/métodos , Mastócitos/citologia , Mastócitos/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Potenciais de Ação , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Comunicação Celular/efeitos dos fármacos , Degranulação Celular/efeitos dos fármacos , Feminino , Mastócitos/efeitos dos fármacos , Ratos , Ratos Long-Evans , Tálamo/citologia , Tálamo/efeitos dos fármacos , Tálamo/fisiologia , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
Single cell unit activity of 187 neurons of 24 rats were analysed to study the possible involvement of intracranial mast cells on modifying thalamic neuronal activity. Mast cells were activated with microiontophoretical application of compound 48/80. This substance did not modify the firing rate of cortical or hippocampal neurons (no mast cells are found here), however it caused excitation (70% in females, 11% in males), or inhibition (7% in females, 33% in males) on thalamic neurons, possibly due to mast cell activation. In consecutive anatomical evaluation many partially or fully degranulated mast cells were found in the recorded thalamic areas.