Efecto de Petiveria alliacea y drogas colinérgicas sobre la habituación / Effects of Petiveria alliacea and cholinergic drugs on the habituation cognitive behavior

Petiveria alliacea (PA) have anxiolytic, antidepressant and cognitive effects. In the present paper the effect of PA water infusion and cholinergic drugs on cognitive behavior were studied. For that, 40 male NMRI mice were divided in 4 groups: Control (n=10), Drug Control (n=10), PA (n=10) and PA plus Drug (n=10). PA 1% was administered orally (7.59±1.39 ml/day); while scopolamine (2 mg/Kg), galantamine (1 mg/Kg) and nicotine (0.1 mg/Kg) were administered intraperitoneally. Behavioral tests included: anxiety maze (AM), open field (OF) and marble burying (MB). Habituation cognitive behavior was evaluated in 4 sessions, one week each session. PA had anxiolytic and antidepressant effect effect in AM, combined with nicotine potentiated an anxiogenic effect in AM, galantamine favored habituation in OF. Scopolamine potentiated the habituation in LA and decreased the obsessive-compulsive behavior in OF. In conclusion; PA had an anxiolytic effect and favored deshabituation, combined with nicotine induced an anxiogenic effect, galantamine favored habituation and scopolamine decreased obsessive-compulsive behavior and favored motor habituation indicated a possible anxiolytic effect.

La Petiveria alliacea (PA) está relacionada con efectos ansiolíticos, antidepresivos y cognitivos. El presente trabajo estudió el efecto de la infusión de PA y drogas colinérgicas sobre la habituación. 40 ratones NMRI machos fueron divididos en 4 grupos: Control (n=10), Control Drogas (n=10), PA (n=10) y PA plus Drogas (n=10). La PA (1%) fue administrada vía oral (7.59±1.39 ml/día); escopolamina (2 mg/Kg), galantamina (1 mg/Kg) y nicotina (0.1 mg/Kg) fueron administrados vía intraperitoneal. Los ensayos conductuales incluyeron: laberinto de ansiedad (LA), campo abierto (CA) y enterramiento aversivo (EA). La habituación fue evaluada en 4 sesiones con duración de una semana cada una. PA mostró un efecto ansiolítico en el LA, combinada con nicotina potenció un efecto ansiogénico en el LA. Galantamina favoreció la habituación en CA, y escopolamina potenció el fenómeno de habituación en LA y disminuyó la conducta obsesivo-compulsiva en CA. En conclusión, la PA mostró un efecto ansiolítico y antidepresivo que potencia la deshabituación, combinada con nicotina indujo un efecto ansiogénico, galantamina favoreció la habituación y escopolamina disminuyó la conducta obsesivo­ compulsiva y favoreció la habituación motora indicando un posible efecto ansiolítico.

Scopolamine reduces the density of M1 muscarinic neurons in rats' hippocampus / La escopolamina reduce la densidad de las neuronas muscarínicas M1 en el hipocampo de ratas

Cholinergic system in CNS is involved in learning and memory. Scopolamine as muscarinic acetylcholine receptor antagonist is used for creation of memory impairment. The purpose of this study is evaluation of scopolamine-based amnesia on memory retention and the effect of this phenomenon on the number of neurons contains M1-receptors in the male Wistar rats hippocampal regions. Thirty-five male Wistar rats (200+/-20 g) were distributed randomly into five groups. Control group (intact samples) and 3 experimental groups with sham group (saline) were tested by the method of passive avoidance (shuttle box) in doses of 0.2, 0.5 and 1 mg/kg (intraperitoneally) as a single dose. After one week, memory test was taken from the rats. Finally, brains dissected from sacrificed rats, and then processed tissues were stained with antibody against M1 receptors (Immunohistochemistry technique) followed by counting of hippocampal CA1, CA3 and DG regions. Our results showed significant decrease in neurons contains M1-receptors in all area of hippocampus. We found that the less number of M1-neurons showed in 1 mg/kg dose of scopolamine. We concluded that scopolamine as muscarinic acetylcholine receptor antagonist can reduce dose-dependently the density of M1-neurons in all areas of hippocampus.

El sistema colinérgico en el SNC está implicado en el aprendizaje y la memoria. La escopolamina como receptor antagonista de acetilcolina muscarínico es utilizada para la creación del deterioro de la memoria. El propósito de este estudio es la evaluación de la amnesia basada en escopolamina sobre la retención de memoria y el efecto de este fenómeno en la cantidad de neuronas en receptores M1 en regiones del hipocampo en ratas macho Wistar. Se distribuyeron al azar, 35 ratas macho Wistar (200+/-20 g) en cinco grupos. El grupo de control (muestras intactas) y 3 grupos experimentales con grupo de tratamiento simulado (solución salina) analizadas por método de evasión pasiva (caja de transporte) en dosis de 0,2; 0,5 y 1 mg/kg (por vía intraperitoneal) como dosis única. Al término de una semana se realizó prueba de memoria de las ratas. Por último, los cerebros diseccionados de las ratas sacrificadas y los tejidos procesados fueron teñidos con anticuerpos contra los receptores M1 (técnica inmunohistoquímica), seguido por el recuento de regiones CA1, CA3 y DG del hipocampo. Nuestros resultados mostraron una disminución significativa en las neuronas con receptores M1 en toda el área del hipocampo. Se encontró que el número menor de neuronas M1, y fue demostrado en 1 mg/kg de dosis de escopolamina. Llegamos a la conclusión de que la escopolamina como antagonista del receptor de acetilcolina muscarínico puede, dependiendo de la dosis, reducir la densidad de neuronas M1 en todas las áreas del hipocampo.

Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats / Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico no tecido hipocampal de ratas ooforectomizadas e controles operadas sem ooforectomia

Different effects of scopolamine on learning, memory, and nitric oxide (NO) metabolites in hippocampal tissues of ovariectomized (OVX) and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco) and OVX-Scopolamine (OVX-Sco) Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001). Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001), while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.

Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico (ON) no tecido hipocampal de ratas ovariectomizadas (OVX) e controles com cirurgia sem ooforectomia (Grupo Sham) foram investigados. Os animais dos grupos Sham-Escopolamina (Sham-Sco) e OVX-Escopolamina (OVX-Sco) foram tratados com escopolamina 2 mg/kg antes de entrar no labirinto aquático de Morris, enquanto aqueles dos grupos Sham e OVX receberam solução salina. A latência de tempo e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Sco e OVX-Sco em comparação com os grupos Sham e OVX, respectivamente (p<0,001). Foram observados níveis significativamente mais baixos de metabólitos do ON nos hipocampos do Grupo Sham-Sco em comparação aos níveis do Sham (p<0,001), enquanto não foi observada diferença significativa entre os Grupos OVX-Sco e OVX. A diminuição do nível de ON no hipocampo pode ter um papel no aprendizado e nos déficits de memória induzidos pela escopolamina. No entanto, parece que este efeito da escopolamina no ON hipocampal é diferente em situações de presença ou ausência de hormônios ovarianos.

Effect of scopolamine-based amnesia on the number of astrocytes in the rat's hippocampus / Efecto de la amnesia inducida por escopolamina sobre el número de astrocitos en el hipocampo de ratas

As neuron­astrocyte interactions play a crucial role in the adult brain, it is thought that astrocytes support learning and memory through specific mechanisms. In this study, the effect of scopolamine based amnesia on the number of astrocytes in rats' hippocampus was studied. Adult male albino Wistar rats were bilaterally cannulated into the CA1 region and animals received saline or different doses of scopolamine (0.5, 1 and 2 mg/ rat, intra - CA1), immediately after training. Then all the rats were sacrificed and coronal sections were taken from the dorsal hippocampal formation of the right cerebral hemispheres and stained with PTAH. The area densities of the astrocytes in dentate gyrus were measured and compared in the all groups (p < 0.05). Data showed that post-training scopolamine (0.5, 1 and 2 ug/rat, intra-CA1) dose-dependently reduced the step-through latency in the inhibitory avoidance task, showing scopolamine-induced amnesia. Also we found different response of astrocytes in different subfields of hippocampal formation. In dentate gyrus the number of astrocytes was increased, but in other areas scopolamine can decreased the density of astrocytes. We concluded that scopolamine can cause amnesia and this phenomenon can have an effect on astrocyte numbers in the rats hippocampal formation.

Las interacciones neuronas-astrocitos desempeñan un papel crucial en el cerebro adulto, y se cree que los astrocitos apoyan el aprendizaje y la memoria a través de mecanismos específicos. Fue estudiado el efecto de amnesia inducida por escopolamina en el número de astrocitos del hipocampo de ratas. Ratas Wistar albinas macho adultas fueron canuladas bilateralmente en la región CA1 recibiendo solución salina o diferentes dosis de escopolamina (0,5, 1 y 2mg/rata, intra - CA1), inmediatamente después del entrenamiento. Luego, todas las ratas se sacrificaron y se tomaron secciones coronales de la formación del hipocampo dorsal del hemisferio cerebral derecho y se tiñeron con PTAH. Las densidades de área de los astrocitos en el giro dentado fueron medidas y comparadas en todos los grupos (p <0,05). Los datos mostraron que la escopolamina (0,5, 1 y 2 mg / rata, intra-CA1) dosis-dependiente post-entrenamiento redujo el paso de latencia de la tarea de evitación inhibitoria, mostrando amnesia inducida por escopolamina. También encontramos diferentes respuestas de los astrocitos en los distintos subcampos de la formación hipocampal. En el giro dentado, el número de astrocitos se incrementó, pero en otras áreas la escopolamina pudo disminuir la densidad de los astrocitos. Se concluye que la escopolamina puede causar amnesia y este fenómeno puede afectar el número astrocitos en la formación hipocampal de ratas.

Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.

Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

[ effect of Atropine, Hyoscine and Promethazine on the duration of labour stages and rate of labour progress in multiparous women]

In most cases, labour is accompanied with pain. Thus, decreasing labour pain is viewed as an important duty of midwives. In this regard, decreasing the duration of labour can be of value. Customarily midwives use drugs to shorten the duration of labour, but the effectiveness of some of the drugs has not been studied systematically. Among such widely used drugs are Atropine, Hyoscine and Promethazine. In this interventional research, the effects of these drugs on labour duration were studied. 160 multiparous women in active phase of labour were selected. 120 of the above women had been administered only one of the above-mentioned drugs and no drug had been administered to the remaining 40. According to the type of drug administered, the women formed three groups, with the women with no drugs administered making the fourth groups. The four groups did not have any statistically significant difference with regard to variables such as age, occupation, education, infant sex, gestational age, infant birth weight, parity, fetal head position, and cervical dilatation at the beginning of our observation. The main result was that, the mean rate of cervical effacement [P<0.05] and descent of fetal head was not significantly different in the 4 groups. But the mean rate of cervical dilatation [P<0.05] was significantly different in four groups. In women who had been given these drugs, the mean rate of cervical dilatation was lower than the women who had not been given any drugs. The mean duration of the first stage of labour was significantly different in four groups [P<0.05]. With regard to the mean duration of the first stage of labour, it was also longer in women who had been given these drugs. The mean rate of second stage of labour and third stage of labour was not significantly different in 4 groups. The use of these drugs can reduce the rate of labour progress and increase the risk of complications, it may also be a waste of prescribed drugs

5-HT3 receptors in selective animal models of cognition.

Role of 5-HT3 receptors in cholinergic hypofunctional models of cognitive impairment in the elevated plus maze model and a passive avoidance model is studied. Cognitive impairment was caused by scopolamine (1 mg/kg, ip) in mice and 5-HT3 ligands mCPBG (1 and 5 mg/kg, ip) and ondansetron (0.5 and 5 mg/kg, ip) were administered before the pre-learning phase to study the effects on acquisition, while post-learning administration was used to determine the effects on consolidation. Ondansetron improved acquisition and retention in cholinergic hypofunctional models while mCPBG potentiated selected impaired cognitive indices. The results indicate the role of 5-HT3 receptors in cognition and that an ideal evaluation of 5-HT3 ligands in cognition should distinguish true cognitive effects from locomotor, motivational and emotional effects.

Revisión de los medicamentos antivertiginosos / a review of antivertigo medication

Objetivo. Valorar la información existente sobre los efectos de las sustancias antivertiginosas, basados en la bibliografía asequible. Información. Se localizaron artículos pertinentes en Medline y en revistas obtenidas en la ciudad de México. Selección del material. Los artículos se seleccionaron en base a su aparente consistencia interna y su relación con el propósito de la revisión. Conclusión. Se evaluaron 22 substancias pertenecientes a 8 grupos farmacológicos (colinérgicos, antihistamínicos, GABAérgicos, bloqueadores de canales de calcio, serotoninérgicos, hemorreológicos, antiagregantes plaquetarios y diuréticos) útiles en diversos padecimientos vertiginosos. Se advirtió la necesidad de un método objetivo y cuantitativo para valorar resultados de ensayos clínicos en humanos. Mientra esto no ocurra, tendremos que usar los medicamentos en base de una información veraz, confiable y basada sólidamente en la farmacología estudiada en experimentos con animales y en la valoración cuidadosa de los efectos -buenos y malos- observados en nuestros pacientes.

Estudio clínico sobre la eficacia y seguridad del 1,3,5, trihidroxibenceno y del 1,3,5, trimetoxibenceno (trifenoles) comparado con butilhioscina en el alivio del dolor cólico de origen intestinal / Efficacy and safety clinical study of 1,3,5, trihydroxibenzene and 1,3,5, trimethoxibenzene (triphenols) compared to butilhioscine in intestinal colic pain

Se realizó un estudio prospectivo, longitudinal, doble ciego aletorio en 184 pacientes con dolor cólico de origen intestinal, con el objetivo de valorar la eficacia y seguridad de dos medicamentos antimuscarínicos, trifenoles en cápsula con 80 mg (86) y butilhioscina con 10 mg (98). Como resultado, en el primer grupo se observó ausencia de dolor en 32 pacientes, leve en 48 y moderado en seis. En el segundo grupo, ausencia de dolor en 42, leve en 45, moderado en nueve y severo en dos. No se presentaron efectos colaterales y en la valoración no hubo diferencias estadísticamente significativa. Por tanto, se puede concluir que ambos fármacos son eficaces y seguros en el alivio del dolor cólico de origen intestinal sin oclusión o suboclusión intestinal

Diclofenac sodium in renal and ureteral colic: a double-blind comparison with hyoscine N-butyl bromide

The analgesic effects of diclofenac 75 mg IM and hyoscine N- buty1 bromide 20 or 40 mg or IV were compared in a randomized double-blind study, in 422 patients reporting moderate to severe pain due to renal or ureteral colic. Patients evaluated their pain intensity and pain relief at 0 [baseline], 15, 30, 45 minutes and hourly for 3 hours. A significant difference [p < 0.05] was found between the two groups with respect to pain intensity difference [PID], mean pain relief and onset time of analgesia. Diclofenac sodium was significantly [p < 0.05] superior to hyoscine N buty1 bromide in pain relief. Significantly [p < 0.05] fewer patents required a second dose in diclofenac sodium treated group compared to the other spasmolytic group. The dose and the route of administration of hyoscine N buty1 bromide had no significant [p > 0.05] effect on the proportion of patients with complete relief. These results confirmed that diclofenac sodium can be safely used in the management of acute renal and ureteral colic as an alternative to hyoscine N buty1 bromide

Possible mechanism of endosulfan-induced enhancement of memory acquisition and retention in mice.

The effects of pre-training and post-training administration of endosulfan on retention of a step-down passive avoidance task was studied in mice. Endosulfan at doses of 1.0 mg/kg(ip) and 2.0 mg/kg(ip) enhanced memory acquisition and retention. This effect of endosulfan was possibly mediated by interaction with cholinergic neurotransmission, as scopolamine (0.5 mg/kg, ip) significantly antagonized the memory enhancing effects of endosulfan. Clonidine (0.05 mg/kg, ip) did not have any effect on enhancement of memory produced by endosulfan, thus indicating possibly no role of noradrenergic system.

(+/-)Baclofen sensitive scopolamine-induced short-term memory deficits in mice.

Possible involvement of GABA receptor systems in scopolamine-induced short-term memory deficits was investigated using latency of mice to reach shock-free zone (SFZ) and number of mistakes (descents) the animal made in 15 min as parameters for acquisition and retention of memory in passive avoidance paradigm. Atropine (1-5 mg/kg), scopolamine (0.1-0.5 mg/kg) but not pirenzepine (5-20 mg/kg) caused disruption of memory. GABA (50, 75 and 100 mg/kg) showed retention enhancing effects in scopolamine-treated and untreated animals but GABA agonist progabide (5-20 mg/kg) did not affect any of the parameter significantly. GABAA agonist, muscimol (0.05 and 0.1 mg/kg) and GABAB agonist, (+/-)baclofen (0.25, 0.5 and 1 mg/kg) and (-)baclofen (0.25 and 0.5 mg/kg) also displayed memory enhancing action. Whereas, GABAA antagonist, bicuculline produced hind limb rigidity, GABAB antagonist, CGP 35348 did not show any effect per se, but reversed the (+/-)baclofen-induced delay in latency, without affecting retention enhancing action of (+/-)baclofen. Combined administration of subeffective dose of GABA (50 mg/kg) and (+/-)baclofen (0.25 mg/kg), showed a significant improvement in acquisition and retention. However, the effect of GABA (100 mg/kg) on acquisition was reversed by bicuculline (2 mg/kg) and by CGP 35348 (100 mg/kg) while improving retention. The present study extends support to the cholinergic concept in cognitive performance and provide an evidence for the influence of GABAergic (particularly GABAB) modulation in scopolamine-induced learning and memory deficits in mice.

Evidence that similar neurotransmitter mechanisms in amygdala, hippocampus and medial septum regulate memory consolidation of avoidance behavior in rats

A injeçäo de ácido DL-amino-5-fosfonopentanóico (AP5) ou escopolamina na amígdala, no septo medial ou no hipocampo, imediatamente após o treino, causa amnésia retrógrada para um aprendizado de esquiva inibitória em ratos. A picrotoxina, no entanto, causa facilitaçäo retrógrada da memória e bloqueia o efeito do AP5 e da escopolamina. O timolol näo tem efeito próprio mas cancela as açöes da picrotoxina. O AP5 é um antagonista de receptores a N-metil-D- aspartato (NMDA) dos aminoácidos excitatórios; a escopolamina é um antagonista dos receptores colinérgicos muscarínicos; a picrotoxina bloqueia o canal de cloro estimulado pelos receptores GABA-A; e o timolol é um antagonista dos ß adrenoreceptores. Os resultados indicam que, na amígdala, no septo medial e no hipocampo, receptores NMDA e muscarínicos säo necessários para a consolidaçäo da memória, receptores GABA-A inibem a açäo dos anteriores, e receptores ß noradrenérgicos modulam a açäo dos receptores GABA-A. A amígdala, o septo medial e o hipocampo operam de forma näo redundante na consolidaçäo da memória

Locomotor activity and one-way active avoidance after intrahyppocampal injection of neurotransmitter antagonists

Sixty-three rats with previous training in a T-maze, bilaterally implanted with cannulae directed toward the dorsal hippocampus, were used in this study. All rats received bilateral 1-microngl injections 20 min before testing for locomotor activity (day 1) and one-way active avoidance (day 3). The following drugs were injected into groups of 4 to 8 animals: scopolamine (9 or 18 microng/micronl), propranolol (5 or 10 microng/micronl), cimetidine (0.75 or 1.5 microng/micronl), sulpiride (5 or 10 microng/micronl), or vehicle (Krebs-ringer). Locomotor activity was not changed by injection of any drug. However, intrahippocampal injections of scolpolamine (9 microng/micronl) and sulpiride (10 microng/micronl) impoaired avoidance bahavior, particularly during the last five trials of the task. We conclude that muscarinic-cholinergic and D2-dopaminergic, but not beta-adrenergic or H2-histaminergic, mechanisms in the hippocampus are involved in the performance of one-way active avoidance behavior

The cholinergic and dopaminergic systems of the prelimbic sector of frontal cortex and memory in the rat

Rats were trained to perform delayed non-matching to sample (a working/representational memory task) and visual discrimination(a reference/dispositional memory task) in a T-maze, and implanted bilaterally with cannulae in the prelimbic cortex. The rats were tested postoperatively after bilateral 1 - micronl injections of vehicle (Krebs-Ringer), sulpiride (10 microng/micronl) or scopolamine (18 microng/micronl). Sulpiride had no effect on the performance of either task, whereas scopolamine interfered only with the performance of delayed non-matching to sample. We conclude that dopaminergic mechanisms in the prelimbic cortex are not involved in either type of memory and that cholinergic, but not dopaminergic, mechanisms are important for working/representational memory process