Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep.

Although Salvia divinorum is traditionally known as a 'mind-altering' or psychoactive herb used, among others things, as a tranquilizer, this property has not been validated with regard to its efficacy and safety. The objective of this study is to provide evidence for the sedative effects of S. divinorum and discriminate the nature of the responsible constituents by examining different experimental models. A battery of tests, including the open-field, hole-board, exploration cylinder, plus-maze and sodium pentobarbital-induced hypnosis potentiation, were used in mice after administration of non-polar, medium polar and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic analysis in rats receiving an active medium polar extract (10 and 100 mg/kg) containing salvinorins was also assessed to study the effects of this plant on sleep architecture. All tested extracts produced significant sedative-like responses, although those of the medium polar extract were more pronounced in mice. The sedative effect of this latter extract, which contains a mixture of salvinorins, caused fragmented sleep architecture in rats by diminishing rapid eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg. Our results provide evidence that S. divinorum exhibits sedative-like depressant properties that alter physiological sleep architecture. Copyright © 2016 John Wiley & Sons, Ltd.

Efecto de las crisis epilépticas parciales y generalizadas sobre la arquitectura del sueño en ratas / Effect of partial and generalised epileptic seizures on sleep architecture in rats

Introducción. La alteración del sueño producido por las crisis epilépticas se conoce; sin embargo, aún se tiene poca información de la alteración en el sueño por el tipo de crisis epiléptica. Materiales y métodos. Se evaluó la arquitectura del sueño de ratas en registros polisomnográficos de 36 horas tras inducirles crisis epilépticas parciales y generalizadas. Para la inducción de las crisis epilépticas se aplicaron in situ 50-100 UI de penicilina G sódica en la amígdala del lóbulo temporal. Resultados. Las crisis parciales y generalizadas provocaron el aumento en la latencia del sueño de ondas lentas (SOL) y sueño de movimiento oculares rápidos (MOR). El número de episodios de las fases de vigilia, SOL y sueño MOR disminuyó y la duración media de los episodios de la vigilia y del SOL aumentó, mientras que la del sueño MOR disminuyó. El porcentaje total del sueño MOR disminuyó significativamente. Durante el primer período de luz, las crisis parciales y generalizadas provocaron el incremento de la vigilia y la reducción de las fases del SOL y sueño MOR. En el período de oscuridad, aumentó el SOL, disminuyó la vigilia y no hubo cambios en el sueño MOR. En el segundo período de luz los porcentajes de las fases de vigilia y SOL regresaron a los valores control y el porcentaje del sueño MOR continuó disminuido. Conclusión. Los cambios en la organización del sueño dependen del tipo de crisis epiléptica que se presenta. Las crisis epilépticas generalizadas provocaron mayor deterioro en el sueño MOR (AU)

Introduction. It is a well-known fact that epileptic seizures disrupt sleep, yet little information is available about sleep disorders according to the type of epileptic seizures. Materials and methods. The sleep architecture of rats was evaluated in polysomnography recordings 36 hours after inducing partial and generalised epileptic seizures in them. The epileptic seizures were induced by applying 50-100 IU of sodium G penicillin in the amygdala of the temporal lobe. Results. Partial and generalised seizures triggered an increase in the latency of slow wave sleep (SWS) and rapid eye movement (REM) sleep. The number of episodes of the phases of wakefulness, SWS and REM sleep was reduced and the mean duration of the episodes of wakefulness and SWS increased, while that of REM sleep diminished. The total percentage of REM sleep diminished signifi cantly. During the first period of light the partial and generalised seizures triggered an increase in wakefulness and a reduction in the phases of SWS and REM sleep. In the period of darkness, the SWS increased and wakefulness decreased, while there were no changes in REM sleep. In the second period of light, the percentages of the phases of wakefulness and SWS returned to control values and the percentage of REM sleep continued to be reduced. Conclusions. Changes in the structuring of sleep depend on the type of epileptic seizure that presents. Generalised epileptic seizures caused greater deterioration in REM sleep (AU)

[Effect of partial and generalised epileptic seizures on sleep architecture in rats]. / Efecto de las crisis epilépticas parciales y generalizadas sobre la arquitectura del sueño en ratas.

INTRODUCTION: It is a well-known fact that epileptic seizures disrupt sleep, yet little information is available about sleep disorders according to the type of epileptic seizures. MATERIALS AND METHODS: The sleep architecture of rats was evaluated in polysomnography recordings 36 hours after inducing partial and generalised epileptic seizures in them. The epileptic seizures were induced by applying 50-100 IU of sodium G penicillin in the amygdala of the temporal lobe. RESULTS: Partial and generalised seizures triggered an increase in the latency of slow wave sleep (SWS) and rapid eye movement (REM) sleep. The number of episodes of the phases of wakefulness, SWS and REM sleep was reduced and the mean duration of the episodes of wakefulness and SWS increased, while that of REM sleep diminished. The total percentage of REM sleep diminished significantly. During the first period of light the partial and generalised seizures triggered an increase in wakefulness and a reduction in the phases of SWS and REM sleep. In the period of darkness, the SWS increased and wakefulness decreased, while there were no changes in REM sleep. In the second period of light, the percentages of the phases of wakefulness and SWS returned to control values and the percentage of REM sleep continued to be reduced. CONCLUSIONS: Changes in the structuring of sleep depend on the type of epileptic seizure that presents. Generalised epileptic seizures caused greater deterioration in REM sleep.

TITLE: Efecto de las crisis epilepticas parciales y generalizadas sobre la arquitectura del sueño en ratas.Introduccion. La alteracion del sueño producido por las crisis epilepticas se conoce; sin embargo, aun se tiene poca informacion de la alteracion en el sueño por el tipo de crisis epileptica. Materiales y metodos. Se evaluo la arquitectura del sueño de ratas en registros polisomnograficos de 36 horas tras inducirles crisis epilepticas parciales y generalizadas. Para la induccion de las crisis epilepticas se aplicaron in situ 50-100 UI de penicilina G sodica en la amigdala del lobulo temporal. Resultados. Las crisis parciales y generalizadas provocaron el aumento en la latencia del sueño de ondas lentas (SOL) y sueño de movimiento oculares rapidos (MOR). El numero de episodios de las fases de vigilia, SOL y sueño MOR disminuyo y la duracion media de los episodios de la vigilia y del SOL aumento, mientras que la del sueño MOR disminuyo. El porcentaje total del sueño MOR disminuyo significativamente. Durante el primer periodo de luz, las crisis parciales y generalizadas provocaron el incremento de la vigilia y la reduccion de las fases del SOL y sueño MOR. En el periodo de oscuridad, aumento el SOL, disminuyo la vigilia y no hubo cambios en el sueño MOR. En el segundo periodo de luz los porcentajes de las fases de vigilia y SOL regresaron a los valores control y el porcentaje del sueño MOR continuo disminuido. Conclusion. Los cambios en la organizacion del sueño dependen del tipo de crisis epileptica que se presenta. Las crisis epilepticas generalizadas provocaron mayor deterioro en el sueño MOR.

Nanoparticle formulation improves the anticonvulsant effect of clonazepam on the pentylenetetrazole-induced seizures: behavior and electroencephalogram.

To document the efficacy of clonazepam (CLZ) either free as a solution or loaded in solid lipid nanoparticles (CLZ-SLN) or mixed micelles (CLZ-MM), the in vitro blood-brain barrier permeability of the formulations was determined. Behavior and/or electroencephalograms (EEGs) of rodents receiving treatments were also studied. The in vitro permeability of CLZ increased when associated with SLN, but decreased in the case of MM. The occurrence of the pentylenetetrazole (PTZ)-induced seizures in mice was significantly prevented by CLZ, even when exposed a lower dose of CLZ-SLN after administration by the oral route. The behavioral severity and EEGs showing the PTZ-induced paroxystic activity in rats diminished significantly in the presence of CLZ alone (0.3 mg/kg), and were almost totally prevented in the rats treated with CLZ-SLN (equivalent to 0.3 mg/kg). The frequency, duration, and spreading of the spikes-wave of rats treated with CLZ-SLN decreased significantly as compared with CLZ alone, CLZ-MM, or the vehicle. These results show an in vitro-in vivo correlation in the enhanced blood-brain barrier permeability of SLN formulation, and a contribution of MM to the carrier effect of drugs toward the bloodstream and brain, where this pharmaceutical formulation of CLZ-SLN improves the anticonvulsant effect of this benzodiazepine, thus offering additional advantages after oral administration.