Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences.http://www.sciencedirect.com/science/article/B6SYS-4S50K2J-1/1/7d11c902193bfa3f1f57030572f7034

Simulating rewetting events in intermittent rivers and ephemeral streams: A global analysis of leached nutrients and organic matter

Climate change and human pressures are changing the global distribution and the ex‐ tent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico‐chemical changes (precon‐ ditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experi‐ mentally simulated, under standard laboratory conditions, rewetting of leaves, river‐ bed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative character‐ istics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dis‐ solved substances during rewetting events (56%–98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contrib‐ uted most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental vari‐ ables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached sub‐ stances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying event

An experimental study of the (J,K)=(3,3) inversion spectral line of NH 3 under the influence of a strong resonant pumping field

A microwave bridge is described which permits radiation from two sources to be propagated through a gas and to be detected separately even when the sources are operating at the same frequency. This bridge is used to study the shape of the (J,K)=(3,3) inversion line in NH when the molecules are subjected to a strong resonant or near-resonant pumping field. The shape of the line is studied by measuring the absorption of a much weaker probe field. For sufficiently strong pump fields, power can be removed from the pump and transferred to the probe field, causing the latter to be amplified. The results are in quantitative agreement with theory. However, the development of a theory which satisfactorily includes the consequences of the degeneracy of the molecular energy levels has not yet been accomplished

Microwave studies of the dynamic Stark shift

A study of the dynamic Stark effect for the (J,K)=(1,1) and (3,3) inversion spectral lines of NH is presented. When the gas in the waveguide absorption cell is strongly driven by off-resonant microwave radiation and probed by a second weak source of radiation, the absorption line profiles are both broadened and shifted. Investigations of this effect in the microwave region have previously been hindered by an inability to separate the weak probe radiation from the strong pump radiation. This experiment uses a balanced-bridge technique to prevent the pump radiation reaching the crystal detector used to monitor the probe radiation. Theoretical calculations of the Stark shifts, which take in to account the variation of electric field across the cell and the M-degeneracy of an inversion level, agree closely with the measured values