The anticonvulsant effect of geraniol and inclusion complex geraniol: beta-cyclodextrin / El efecto anticonvulsivo de geraniol y la inclusión de geraniol complejo: beta-ciclodextrina

Geraniol (GR) is an acyclic monoterpene alcohol present in essential oils of aromatic plant species used in Brazilian folk medicine for the treatment of epilepsy. The present study was designed to evaluate the anticonvulsant effect of GR and of the inclusion complex geraniol:beta-cyclodextrin (GR:beta-CD). Mice were treated with GR or with GR:beta-CD (50, 100 and 200 mg/kg) 30 min before pentylenetetrazole (PTZ) or strychnine (STN). GR at 200 mg/kg and GR:beta-CD at the doses of 100 and 200 mg/kg significantly increased the latency for the first PTZ-induced convulsion and reduced the percentage of animals that convulsed. The pretreatment of flumazenil did not revert the anticonvulsant effect of GR in the PTZ-induced convulsion model. In the STN-induced convulsion model, the effects of GR were investigated and no difference was found against control. The results demonstrated an anticonvulsant activity of GR in the PTZ-model, which was potentialized by the complexation with beta-CD...

Geraniol (GR) es un alcohol monoterpeno acíclico presentes en los aceites esenciales de las especies de plantas aromáticas utilizadas en la medicina popular brasileña para el tratamiento de la epilepsia. El presente estudio fue diseñado para evaluar el efecto anticonvulsivo del GR y de la inclusión de geraniol complejo: beta-ciclodextrina (GR:beta-CD). Los ratones fueron tratados con GR o con GR:beta- CD (50, 100 y 200 mg/kg) 30 minutos antes de pentylenotetrazole (PTZ) o strichinine (STN). GR a 200 mg/kg y GR:beta-CD en las dosis de 100 y 200 mg/kg aumentó significativamente la latencia para la primera convulsión inducida PTZ-y redujo la porcentaje de animales que convulsionó. El tratamiento previo de flumazenil no revirtió el efecto anticonvulsivo de GR en el modelo de convulsión inducida con PTZ. En el modelo de convulsión inducida com STN, los efectos de GR fueron investigados y no se encontró ninguna diferencia contra el control. Los resultados demostraron una actividad anticonvulsiva de geraniol en el modelo de PTZ, que fue potenciada por la formación de complejos con beta-CD...

Activación del sistema de los opiodes endógenos por dosis subconvulsivamantes de metrazol / Activation of the endogenous opioid system with metrazol subconvulsivant dosis

Se investigaron las alteraciones en el sistema de los opioides endógenos en el cerebro de la rata, inducidas por la administración de una dósis subconvulsivante de metrazol (PTZ) (30 mg/kg i.p.). Por medio de experimentos de microdiálisis, encontramos durante los primeros 60 min después del tratamiento, una liberación importante de opiodes endógenos en el hipocampo y la amígdala cerebral. Posteriormente, los valores regresaron a los niveles basales. Por autorradiografía se observó un decremento en los niveles de los receptores mu en varias estructuras cerebrales. Mediante el análisis de la unión a receptores las membranas cerebrales, se confirmó un decremento en el número de estos receptores, sin cambios en su afinidad. En la aplicación de la prueba de Randall-Sellito, se encontró un aumento en el umbral de respuesta a estímulos dolorosos, durante los primeros 30 min. después del PTZ. Finalmente, experimentos de hibridación in situ revelaron un incremento en los niveles de la proencefalina a las 24 hrs después del tratamiento. Nuestros resultados indican que la administración de dosis subconvulsivante de PTZ activan de manera importante al sistema de los opiodes endógenos. Estos cambios resultan relevantes para entender el proceso del epileptogénesis y los mecanismos involucrados en el mismo

Behavioral and pharmacological validation of the elevated plus maze contructed with transparent walls

In this study we compared the performance of male Wistar rats, weighing 250-300g, submitted to the standard plus maze (vertical surfaces of the closed arms with opaque walls) to their performance in a modified maze with raised Plexiglas edges in the closed arms (transparent walls). The animals (N = 12 for each group) continued to show a clear preference for the closed arms with transparent walls of the modified elevated plus maze. In addition, exploratory activity was higher in the open arms of the modified plus maze (4.25 ñ 0.42 entries and 53.50 ñ 5.10s) as compared to that of the standard plus maze (2.10 ñ 0.25 entries and 24.00 ñ 4.91 s). Intraperitoneal injection of midazolam produced an increase in the number of entries (6.40 ñ 1.21 and 8.50 ñ 1.15 for 1.0 and 2.0 mg/Kg, rspectively) and in the time spent in the open arms (85.32 ñ 14.56 and 125.50 ñ 22.16 s for 1.0 and 2.0 mg/Kg, respectively) while pentylenetetrazole caused a decrease in the number of entries (3.68 ñ 0.54 and 2.33 ñ 0.62 for 5.0 and 10 mg/Kg, respectively) and in the time spent in the open arms of the modified maze (39.60 ñ 6.67 and 23.60 ñ 6.40 s for 5.0 and 10 mg/Kg, respectively). The anxiolytic effect of midazolam and the anxiogenic effect of pentylenetetrazole were similar to those usually reported in the literature by authors using the standard test. The4se results behaviorally and pharmacologically validate the elevated plus maze with transparebnt walls and suggest that this test could be a useful tool for the study of anxiolytic drugs and the neurobiology of anxiety

Anxiety-induced antinociception in the mouse

It has been suggested that exposure to the elevated plus-maze (EPM) apparatus induces antinociceptive effects in mice as measured by the tail-flick assay,, which are not blocked by the opiate antagonist naltrexone. The a) if exposure limited to the open or the enclosed arm of the EPM would alter this effect; b) whether or not pharmacologically induced anxiety (1.0 mg/kg pentylenetetrazole, PTZ) would also reduce nociceptions: c) if exposure to the EPM would alter visceral pain, as measured by the abdominal contortion test. The simultaneous exposure to both the open and enclosed arms of the EPM, but not the exposure limited to each type of arm, led to statistically significant increases in tail withdrawal latencies (TWL). Indeed, 10 min after exposure to both arms, TWL values (means ñ SEM) were 10.31 ñ 0.87 s as compared to a baseline value of 5.46 ñ 0.53 s. The acute administration of PTZ significantly increased TWL. Conversely, EPM-induced antinociception was not detected by the abdominal contortion test. These results confirm the existence of EPM-induced antinociceptive effects demonstrated by others and show that they may be multiple determinants

Breathing pattern during pharmacological activation and blockade of the intermediate area of the ventrolateral surface of the cat medulla

The present study analyzes the respiratory pattern of chloralose- (50-60 mg/kg,iv) anesthetized cats treated with Nembutal (NE) (30 mg/ml), glycine (GL) (200 mg/ml) or leptazol (LE) (200 mg/ml) topically applied to the intermediate area of the ventrolateral surface of the medulla oblongata in a volume of 20 micronl. Application of NE and GL produced a decrease in ventilation (-24%) and tidal volume (-25%) suggesting that the intermediate area facilitates respiratory drive and inhibits the inspiratory off-switch mechanism. These results are consistent with the view that intermediate area is necessary for the central chemosensitivity to CO2. The topical application of LE produced an increase in inspiration time (12.5%), expiration time (20.8%) and tidal volume (7%). The increased tidal volume caused by LE is compatible with it action as a GL antagonist