Synedrella nodiflora extract depresses excitatory synaptic transmission and chemically-induced in vitro seizures in the rat hippocampus

Extracts of the tropical Cinderella plant Synedrella nodiflora are used traditionally to manage convulsive conditions in the West African sub-region. This study sought to determine the neuronal basis of the effectiveness of these plant extracts to suppress seizure activity. Using the hippocampal slice preparation from rats, the ability of the extract to depress excitatory synaptic transmission and in vitro seizure activity were investigated. Bath perfusion of the hydro-ethanolic extract of Synedrella nodiflora (SNE) caused a concentration-dependent depression of evoked field excitatory postsynaptic potentials (fEPSPs) recorded extracellularly in the CA1 region of the hippocampus with maximal depression of about 80% and an estimated IC50 of 0.06 mg/ml. The SNE-induced fEPSP depression was accompanied by an increase in paired pulse facilitation. The fEPSP depression only recovered partially after 20 min washing out. The effect of SNE was not stimulus dependent as it was present even in the absence of synaptic stimulation. Furthermore, it did not show desensitization as repeat application after 10 min washout produced the same level of fEPSP depression as the first application. The SNE effect on fEPSPs was not via adenosine release as it was neither blocked nor reversed by 8-CPT, an adenosine A1 receptor antagonist. In addition, SNE depressed in vitro seizures induced by zero Mg2+ and high K+ -containing artificial cerebrospinal fluid (aCSF) in a concentration-dependent manner. The results show that SNE depresses fEPSPs and spontaneous bursting activity in hippocampal neurons that may underlie its ability to abort convulsive activity in persons with epilepsy

Anticonvulsant and related neuropharmacological effects of the whole plant extract of Synedrella nodiflora (L.) Gaertn (Asteraceae)

Purpose: The plant Synedrella nodiflora (L) Gaertn is traditionally used by some Ghanaian communities to treat epilepsy. To determine if this use has merit, we studied the anticonvulsant and other neuropharmacological effects of a hydro-ethanolic extract of the whole plant using murine models. Materials and Methods: The anticonvulsant effect of the extract (10-1000 mg/kg) was tested on the pentylenetetrazole-, picrotoxin-, and pilocarpine-induced seizure models and PTZ-kindling in mice/rats. The effect of the extract was also tested on motor coordination using the rota-rod. Results: The results obtained revealed that the extract possesses anticonvulsant effects in all the experimental models of seizures tested as it significantly reduced the latencies to myoclonic jerks and seizures as well as seizure duration and the percentage severity. The extract was also found to cause motor incoordination at the higher dose of 1000 mg/kg. Conclusions: In summary, the hydro-ethanolic extract of the whole plant of S. nodiflora possesses anticonvulsant effects, possibly through an interaction with GABAergic transmission and antioxidant mechanisms and muscle relaxant effects. These findings thus provide scientific evidence in support of the traditional use of the plant in the management of epilepsy

Pharmaceutical Care Education in Kuwait: Pharmacy Students Perspectives

Background: Pharmaceutical care is defined as the responsible provision of medication therapy to achieve definite outcomes that improve patients’ quality of life. Pharmacy education should equip students with the knowledge, skills, and attitudes they need to practise pharmaceutical care competently.Objective: To investigate pharmacy students’ attitudes towards pharmaceutical care, perceptions of their preparedness to perform pharmaceutical care competencies, opinions about the importance of the various pharmaceutical care activities, and the barriers to its implementation in Kuwait.Methods: A descriptive, cross-sectional survey of pharmacy students (n=126) was conducted at Faculty of Pharmacy, Kuwait University. Data were collected via a pre-tested self-administered questionnaire. Descriptive statistics including percentages, medians and means Likert scale rating (SD) were calculated and compared using SPSS, version 19. Statistical significance was accepted at a p value of 0.05 or lower.Results: The response rate was 99.2%. Pharmacy students expressed overall positive attitudes towards pharmaceutical care. They felt prepared to implement the various aspects of pharmaceutical care, with the least preparedness in the administrative/management aspects. Perceived pharmaceutical care competencies grew as students progressed through the curriculum. The students also appreciated the importance of the various pharmaceutical care competencies. They agreed/strongly agreed that the major barriers to the integration of pharmaceutical care into practice were lack of private counseling areas or inappropriate pharmacy layout (95.2%), lack of pharmacist time (83.3%), organizational obstacles (82.6%), and pharmacists’ physical separation from patient care areas (82.6%).Conclusion: Pharmacy students’ attitudes and perceived preparedness can serve as needs assessment tools to guide curricular change and improvement. Student pharmacists at Kuwait University understand and advocate implementation of pharmaceutical care while also recognizing the barriers to its widespread adoption. The education and training provided at Kuwait University Faculty of Pharmacy is designed to develop students to be the change agents who can advance pharmacist-provided direct patient care

17\u3b2-estradiol attenuates excitatory neurotransmission and enhances the excitability of rat parabrachial neurons in vitro

The steroid hormone 17\u3b2-estradiol and its respective receptors have been found in several cardiovascular nuclei in the central nervous system including the parabrachial nucleus. In a previous study, we provided evidence that 17\u3b2-estradiol attenuated an outward potassium conductance in parabrachial neurons of male rats, using an in vitro slice preparation. In this study we sought to enhance the comprehensive information provided previously on estradiol's postsynaptic effects in the parabrachial nucleus by directly examining whether 17\u3b2-estradiol application will modulate excitatory synaptic neurotransmission. Using a pontine slice preparation and whole-cell patch-clamp recording, bath application of either 17\u3b2-estradiol (20\u2013100 \u3bcM) or BSA-17\u3b2-estradiol (50 \u3bcM) decreased the amplitude of evoked excitatory postsynaptic currents (from 30\u201360% of control) recorded from neurons in the parabrachial nucleus. The paired pulse ratio was not significantly affected and suggests a post-synaptic site of action. The inhibitory effect on the synaptic current was relatively long-lasting (non-reversible) and was blocked by the selective estrogen receptor antagonist, ICI 182,780. Furthermore, 17\u3b2-estradiol reduced the maximum current elicited by a ramp protocol, increased the input resistance measured between resting membrane potential and action potential threshold and caused an increase in the firing frequency of the cells under current-clamp. In summary, 17\u3b2-estradiol caused 3 effects: first, a depolarization; second, a reduction in evoked excitatory postsynaptic potentials; and third, an enhancement of action potential firing frequency in neurons of the parabrachial nucleus. These observations are consistent with our previous findings and support a role for estrogen in modulating neurotransmission in this nucleus.Peer reviewed: YesNRC publication: Ye

Cocaine sensitization does not alter SP effects on locomotion or excitatory synaptic transmission in the NAc of rats

Substance P (SP) and cocaine employ similar mechanisms to modify excitatory synaptic transmission in the nucleus accumbens (NAc), a region implicated in substance abuse. Here we explored, using NAc slices, whether SP effects on these synaptic responses were altered in rats that have been sensitized to cocaine and whether SP could mimic cocaine in triggering increased locomotion in sensitized rats. Intraperitoneal (IP) injection of na\uefve rats with cocaine (15 mg/kg) caused increased locomotion by 408.5 \ub1 85.9% (n = 5) which further increased by 733.1 \ub1 157.8% (n = 5) following a week of cocaine sensitization. A similar challenge with 10 mg/kg of SP after cocaine sensitization did not produce significant changes in locomotion (170.6 \ub1 61.0%; n = 4). In contrast to cocaine, IP injection of rats with SP or SP5\u201311 (10\u2013100 mg/kg) with or without phosphoramidon did not elicit changes in locomotion. In electrophysiological studies, both cocaine and SP depressed evoked NMDA and non-NMDA receptor-mediated excitatory synaptic currents (EPSCs) in slices obtained from na\uefve rats. In slices derived from cocaine-sensitized rats, cocaine but not SP produced a more profound decrease in non-NMDA compared to NMDA responses. Similar to that in na\uefve rats, cocaine\u2019s effect on the EPSCs in these sensitized rats occluded those of SP. Thus, although SP and cocaine may employ similar mechanisms to depress EPSCs in the NAc, IP injection of SP does not mimic cocaine-induced hyperlocomotion indicating that not all of cocaine\u2019s effects are mimicked by SP.Peer reviewed: YesNRC publication: Ye

Substance P and cocaine employ convergent mechanisms to depress excitatory synaptic transmission in the rat nucleus accumbens in vitro

Substance P (SP) has been reported to produce effects on excitatory synaptic transmission in the nucleus accumbens (NAc) that are similar to those induced by cocaine. To address the question of whether SP serves as an endogenous mediator producing cocaine-like effects that are known to be D1-receptor-mediated, we tested the hypothesis that the effects of SP and cocaine on excitatory postsynaptic currents (EPSCs) in the NAc occlude one another.Wereport here that SP and SP5\u201311 actions occlude the effect of cocaine and vice versa. SP, SP5\u201311 and cocaine all depressed evoked, non-N-methyl-d-aspartate (NMDA) receptor-mediated synaptic currents in a concentration-dependent manner, with EC50 values of 0.12, 0.17 and 8.3 lm, respectively. Although cocaine was the least potent, it was most efficacious. SP, SP5\u201311 and cocaine all suppressed isolated NMDA receptor-mediated evoked EPSCs. SP5\u201311 (1 lm)-induced EPSC depression was blocked by the neurokinin-1 antagonist L732138 and by the D1-like receptor antagonist SCH23390. Pretreatment of slices with cocaine (30 lm) depressed the EPSC by 39.1% \ub1 4.8%. Application of SP or SP5\u201311 (1 lm) at the peak of the cocaine depressive effect on theEPSCdid not produce any additional diminution of the response (5.7% \ub1 2.8%). In the reverse experiments, in which either SP or SP5\u201311 was applied first, subsequent application of cocaine at the peak of the peptide\u2019s effect (30.3% \ub1 2.3%) produced a further but smaller depression (15.5% \ub1 3.6%) of the remaining EPSC. These data indicate that cocaine and SP produce similar effects on excitatory synaptic transmission in the NAc, and that their actions occlude one another. This suggests that SP may act like cocaine in its absence, and may be an endogenous trigger for the reward and behaviors associated with cocaine.On a observ\ue9 que la substance P (SP) avait des effets semblables \ue0 ceux de la coca\uefne sur la transmission synaptique excitatrice dans le noyau accumbens (NAc). Afin de d\ue9terminer si la SP agit comme un m\ue9diateur endog\ue8ne et a des effets semblables \ue0 ceux de la coca\uefne, dont on sait qu\u2019ils sont m\ue9di\ue9s par les r\ue9cepteurs dopaminergiques D1, nous avons cherch\ue9 \ue0 v\ue9rifier l\u2019hypoth\ue8se selon laquelle la SP bloque les effets de la coca\uefne sur les courants postsynaptiques excitateurs dans le NAc, et vice versa. Nous avons observ\ue9 dans le cadre de nos travaux que la SP et le peptide SP5\u201311 bloquent l\u2019effet de la coca\uefne, et inversement. La SP, le peptide SP5\u201311 et la coca\uefne ont tous provoqu\ue9 une d\ue9pression des courants synaptiques \ue9voqu\ue9s m\ue9di\ue9s par des r\ue9cepteurs non NMDA (N-m\ue9thyl-D-aspartate), effet qui \ue9tait fonction de la concentration; les CE50 \ue9taient de 0,12, 0,17 et 8,3 \u3bcm, respectivement. Bien que la coca\uefne ait \ue9t\ue9 la moins active de ces substances, elle s\u2019est r\ue9v\ue9l\ue9e \ueatre la plus efficace. La SP, le peptide SP5\u201311 et la coca\uefne ont tous les trois supprim\ue9 des courants postsynaptiques excitateurs isol\ue9s \ue9voqu\ue9s par des r\ue9cepteurs NMDA. La d\ue9pression des courants postsynaptiques excitateurs induite par le peptide SP5\u201311 (1 \u3bcm) a \ue9t\ue9 bloqu\ue9e par la mol\ue9cule L732138, un antagoniste de la neurokinine-1, et par la mol\ue9cule SCH23390, un antagoniste des r\ue9cepteurs de type D1. Le pr\ue9traitement des coupes par la coca\uefne (30 \u3bcm) a d\ue9prim\ue9 le courant postsynaptique excitateur de 39,1 % \ub1 4,8 %. L\u2019application de la SP ou du peptide SP5\u201311 (1 \u3bcm) au moment o\uf9 l\u2019effet d\ue9pressif de la coca\uefne sur le courant postsynaptique excitateur \ue9tait \ue0 son maximum n\u2019a provoqu\ue9 aucune diminution additionnelle de la r\ue9ponse (5,7 % \ub1 2,8 %). Dans les exp\ue9riences inverses, o\uf9 l\u2019on appliquait d\u2019abord la SP ou le peptide SP5\u201311, l\u2019application de la coca\uefne au moment o\uf9 l\u2019effet de la SP ou du peptide \ue9tait \ue0 son maximum (30,3 % \ub1 2,3 %) a entra\ueen\ue9 une d\ue9pression additionnelle, quoique l\ue9g\ue8re (15,5 % \ub1 3,6 %), du courant postsynaptique excitateur restant. Selon ces donn\ue9es, la coca\uefne et la SP ont un effet similaire sur la transmission synaptique excitatrice dans le NAc et se bloquent mutuellement. Ceci donne \ue0 penser que la SP peut agir comme la coca\uefne en l\u2019absence de celle-ci et servir de d\ue9clencheur endog\ue8ne du circuit de la r\ue9compense et des comportements associ\ue9s \ue0 la coca\uefne.Peer reviewed: YesNRC publication: Ye