Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats

Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either i.p. saline, mephedrone (10mg/kg), caffeine (10mg/kg) or combined caffeine and mephedrone twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day two), elevated plus maze (EPM, day eight) exploration, rectal temperature changes (day nine) and prepulse inhibition of acoustic startle (PPI, day 15) response were assessed. Seven days after the final injection, brain regions were collected for measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs

Recursion Relations for One-Loop Gravity Amplitudes

We study the application of recursion relations to the calculation of finite one-loop gravity amplitudes. It is shown explicitly that the known four, five, and six graviton one-loop amplitudes for which the external legs have identical outgoing helicities, and the four graviton amplitude with helicities (-,+,+,+) can be derived from simple recursion relations. The latter amplitude is derived by introducing a one-loop three-point vertex of gravitons of positive helicity, which is the counterpart in gravity of the one-loop three-plus vertex in Yang-Mills. We show that new issues arise for the five point amplitude with helicities (-,+,+,+,+), where the application of known methods does not appear to work, and we discuss possible resolutions.Comment: 28 pages, LaTeX, 12 figures. v2:typos and references correcte

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Near-zero humidities on Ben Nevis, Scotland, revealed by pioneering 19th-century observers and modern volunteers

The weather on Ben Nevis – the highest mountain in the British Isles, 1345 m AMSL – sometimes shows episodes of remarkably low relative humidity (RH) with few precedents anywhere else in the British Isles. We are able to quantify this for the first time using a high-quality series of hourly dry- and wet-bulb observations, made on the summit. These observations were made between 1883 and 1904, but have only just become available to modern science, thanks to thousands of volunteers who worked to rescue this unique and exemplary dataset from published volumes. Careful examination and analysis of the original observations using modern psychrometric theory revealed several occasions where we are confident that the summit RH fell close to zero as a result of anticyclonic subsidence. Three case histories are examined in some detail. The nineteenth-century Ben Nevis humidity records are also compared with contemporary automatic weather station (AWS) data from two high-altitude Scottish mountain sites

Dielectrophoresis of charged colloidal suspensions

We present a theoretical study of dielectrophoretic (DEP) crossover spectrum of two polarizable particles under the action of a nonuniform AC electric field. For two approaching particles, the mutual polarization interaction yields a change in their respective dipole moments, and hence, in the DEP crossover spectrum. The induced polarization effects are captured by the multiple image method. Using spectral representation theory, an analytic expression for the DEP force is derived. We find that the mutual polarization effects can change the crossover frequency at which the DEP force changes sign. The results are found to be in agreement with recent experimental observation and as they go beyond the standard theory, they help to clarify the important question of the underlying polarization mechanisms

Proton propagation in nuclei studied in the (e,e’p) reaction

Proton propagation in nuclei was studied using the (e,e’p) reaction in the quasifree region. The coincidence (e,e’p) cross sections were measured at an electron angle of 50.4° and proton angles of 50.1°, 58.2°, 67.9°, and 72.9° for 12C, 27Al, 58Ni, and 181Ta targets at a beam energy of 779.5 MeV. The average outgoing proton energy was 180 MeV. The ratio of the (e,e’p) yield to the simultaneously measured (e,e’) yield was compared to that calculated in the plane-wave impulse approximation and an experimental transmission defined. These experimental transmissions are considerably larger (a factor of ∼2 for 181Ta) than those one would calculate from the free N-N cross sections folded into the nuclear density distribution. A new calculation that includes medium effects (N-N correlations, density dependence of the N-N cross sections and Pauli suppression) accounts for this increase

Orientifolds of K3 and Calabi-Yau Manifolds with Intersecting D-branes

We investigate orientifolds of type II string theory on K3 and Calabi-Yau 3-folds with intersecting D-branes wrapping special Lagrangian cycles. We determine quite generically the chiral massless spectrum in terms of topological invariants and discuss both orbifold examples and algebraic realizations in detail. Intriguingly, the developed techniques provide an elegant way to figure out the chiral sector of orientifold models without computing any explicit string partition function. As a new example we derive a non-supersymmetric Standard-like Model from an orientifold of type IIA on the quintic Calabi-Yau 3-fold with wrapped D6-branes. In the case of supersymmetric intersecting brane models on Calabi-Yau manifolds we discuss the D-term and F-term potentials, the effective gauge couplings and the Green-Schwarz mechanism. The mirror symmetric formulation of this construction is provided within type IIB theory. We finally include a short discussion about the lift of these models from type IIB on K3 to F-theory and from type IIA on Calabi-Yau 3-folds to M-theory on G_2 manifolds.Comment: 82 pages, harvmac, 5 figures. v2: references added. v3: T^6 orientifold corrected, JHEP versio

A Quantitative Model of Energy Release and Heating by Time-dependent, Localized Reconnection in a Flare with a Thermal Loop-top X-ray Source

We present a quantitative model of the magnetic energy stored and then released through magnetic reconnection for a flare on 26 Feb 2004. This flare, well observed by RHESSI and TRACE, shows evidence of non-thermal electrons only for a brief, early phase. Throughout the main period of energy release there is a super-hot (T>30 MK) plasma emitting thermal bremsstrahlung atop the flare loops. Our model describes the heating and compression of such a source by localized, transient magnetic reconnection. It is a three-dimensional generalization of the Petschek model whereby Alfven-speed retraction following reconnection drives supersonic inflows parallel to the field lines, which form shocks heating, compressing, and confining a loop-top plasma plug. The confining inflows provide longer life than a freely-expanding or conductively-cooling plasma of similar size and temperature. Superposition of successive transient episodes of localized reconnection across a current sheet produces an apparently persistent, localized source of high-temperature emission. The temperature of the source decreases smoothly on a time scale consistent with observations, far longer than the cooling time of a single plug. Built from a disordered collection of small plugs, the source need not have the coherent jet-like structure predicted by steady-state reconnection models. This new model predicts temperatures and emission measure consistent with the observations of 26 Feb 2004. Furthermore, the total energy released by the flare is found to be roughly consistent with that predicted by the model. Only a small fraction of the energy released appears in the super-hot source at any one time, but roughly a quarter of the flare energy is thermalized by the reconnection shocks over the course of the flare. All energy is presumed to ultimately appear in the lower-temperature T<20 MK, post-flare loops