Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice

Context—Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. Objective—To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. Materials and methods—Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests.Context—Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. Objective—To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. Materials and methods—Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests

MLearn 08 : the bridge from text to context

Abstract onlyINFONET-BioVision.org is an freely available internet based knowledge-management system, funded by the Liechtenstein Development Service (LDS) and the BioVision Foundation for Environment and Development, that offers Kenyan farmers information on affordable, effective and ecologically sound technologies in crop and livestock production as well as environmental and human health. One of the challenges faced by the project is the secure provision of information to the rural areas that would most benefit from advice on crop pests and productivity [Avallain, 2008] . Bandwidth is sometimes available in these areas, but is limited, unmanaged and relatively expensive. This paper discusses current work in the development of a novel system that brings together hardware and software to make better use of available bandwidth, whilst offering a financially viable and sustainable method of extending internet provision to these hard-to-reach areas, providing rural farmers with access to the INFONET-BioVision platform and other internet based sources of information. The system currently in development is premised on the fact that some internet based applications require more bandwidth than others. Moreover, their real-time requirements differ greatly. Although it is conceivable that a number of users can share low-bandwidth connections, the multiple bandwidth requests created can easily overwhelm the connection due to the way in which these are managed by protocols developed for bandwidth-rich countries. This results in virtually no bandwidth availability for the user applications themselves. It is clear, therefore, that to maximise the number of users on one low-bandwidth connection, allocation should take place before applications actually make the bandwidth requests. Indeed, similar bandwidth management exists on a larger scale, with domestic broadband providers controlling the amount of data provided through existing channels to a home user at the exchange, based on a tariff system. The system effectively applies a scaled down version of this scenario to available connectivity, be that GPRS, satellite or wired. An inexpensive single-board computer acts as a hub between users and internet, allowing software management of bandwidth and connectivity to users mobile devices through Wi-Fi, Bluetooth and wired LAN. The allocation of bandwidth to each user is based on a voucher system that effectively splits the cost of the connection. Users purchase these vouchers, which are priced according to usage, ranging from very low, none real-time e-mail access to more expensive web-browsing, prior to accessing the system. The proposed system is intended to provide communities with inexpensive connectivity through shared costs which is scaleable, such that, should there be a requirement for extra provision of bandwidth or number of users, subsequent devices can be added or moved simply, easily and at low cost. The system is scheduled for testing later in 2008, at which point a full evaluation will be undertaken

The mGluR5 antagonist fenobam induces analgesic conditioned place preference in mice with spared nerve injury

Antagonists of metabotropic glutamate receptors (mGluRs) have the potential to act as analgesic drugs that may help alleviate chronic pain. This study was done to look at the possible rewarding properties of the mGluR5 antagonist, fenobam, in a cognitive assay. Analgesic conditioned place preference (aCPP) was used to examine the effects of fenobam (30 mg/kg) and the prototypical mGluR5 antagonist, MPEP, and these effects were compared to those of a drug with known analgesic properties, morphine (10 mg/kg). In each experiment, one group of mice received spared nerve injury (SNI) surgery to model chronic pain; the other group received a control sham surgery. Both fenobam and MPEP induced preference in the SNI mice, such that SNI mice spent significantly more time in the mGluR5 antagonist-paired chamber compared to a vehicle-paired chamber. No such preference developed for sham mice. Morphine induced preference in male and female mice in both the SNI and sham groups. The results showed that fenobam and MPEP likely reduced on-going distress in the SNI mice, causing them to prefer the chamber paired with the drug compared to the vehicle-paired chamber. Since sham animals did not prefer the drug-paired chamber, these data demonstrate that mGluR5 antagonism is non-rewarding in the absence of pain-like injury. © 2014 Lax et al

MPEP induces place preference in male SNI mice only.

<p>(<b>A</b>) SNI mice (n = 8) spent significantly more total time in the MPEP-paired chamber compared to vehicle-paired chamber on post-conditioning day 5. (<b>B</b>) Sham mice (n = 8) show no difference in the total amount of time spent in MPEP and vehicle-paired chamber on post-conditioning day 5. (<b>C</b>) SNI mice increase the amount of time they spend in the MPEP-paired chamber on day 5 (post-conditioning) compared to baseline (day 1 pre-conditioning) while (<b>D</b>) sham mice show no such difference. Paired t-test, *p<0.05, **p<0.01.</p

Male SNI and sham mice travel similar distances and show tolerance to locomotor side-effects.

<p>(<b>A</b>) SNI (n = 15) and sham (n = 15) mice travel a similar distance in both outer chambers of the aCPP apparatus on preconditioning day 1. (<b>B</b>) On conditioning day 2 and (<b>C</b>) conditioning day 3, both SNI and sham mice are hyperactive when treated with fenobam. Mice were restricted to only one of the outer chambers when these measurements were taken. (<b>D</b>) However, by day 4, neither group of mice show increased distance traveled in the fenobam chamber compared to the vehicle-paired chamber. Two-way ANOVA followed by Bonferroni <i>post hoc</i> test, **p<0.01, ***p<0.001.</p

Morphine induces place preference in all male mice.

<p>(<b>A</b>) SNI mice (n = 9) spend significantly more total time in the morphine-paired chamber compared to vehicle-paired chamber on post-conditioning day 5. (<b>B</b>) Sham mice (n = 15) showed a similar significant preference. (<b>C</b>) SNI mice increase the amount of time they spent in the morphine-paired chamber on day 5 (post-conditioning) compared to baseline (day 1 pre-conditioning) while (<b>D</b>) sham mice showed a similar significant preference. Paired t-test, *p<0.05, **p<0.01.</p

Fenobam induces place preference in male SNI mice only.

<p>(<b>A</b>) SNI mice (n = 15) spent significantly more total time in the fenobam-paired chamber compared to vehicle-paired chamber on post-conditioning day 5. (<b>B</b>) Sham mice (n = 15) show no difference in the total amount of time spent in fenobam and vehicle-paired chamber on post-conditioning day 5. (<b>C</b>) SNI mice increase the amount of time they spent in the fenobam-paired chamber on day 5 (post-conditioning) compared to baseline (day 1 pre-conditioning) while (<b>D</b>) sham mice show no such difference. Paired t-test, *p<0.05, **p<0.01.</p

Morphine induces place preference in all female mice.

<p>(<b>A</b>) SNI mice (n = 5) spend significantly more total time in the morphine-paired chamber compared to vehicle-paired chamber on post-conditioning day 5. (<b>B</b>) Sham mice (n = 6) show a similar significant preference. (<b>C</b>) SNI mice increase the amount of time they spent in the morphine-paired chamber on day 5 (post-conditioning) compared to baseline (day 1 pre-conditioning). (<b>D</b>) Sham mice show a similar significant preference. Paired t-test, *p<0.05, **p<0.01, ***p<0.001.</p

Fenobam induces place preference in female SNI mice only.

<p>(<b>A</b>) SNI mice (n = 10) spent significantly more total time in the fenobam-paired chamber compared to vehicle-paired chamber on post-conditioning day 5. (<b>B</b>) Sham mice (n = 11) show no difference in the total amount of time spent in fenobam and vehicle-paired chamber on post-conditioning day 5. (<b>C</b>) SNI mice increase the amount of time they spend in the fenobam-paired chamber on day 5 (post-conditioning) compared to baseline (day 1 pre-conditioning) while (<b>D</b>) sham mice show no such difference. Paired t-test, *p<0.05, **p<0.01.</p