Effects of methamphetamine-induced neurotoxicity on striatal long-term potentiation.

Rationale: Methamphetamine (METH) exposure is associated with damage to central monoamine systems, particularly dopamine signaling. Rodent models of such damage have revealed a decrease in the amplitude of phasic dopamine signals and significant striatal dysfunction, including changes in the molecular, system, and behavioral functions of the striatum. Dopamine signaling through D1 receptors promotes corticostriatal long-term potentiation (LTP), a critical substrate of these striatal functions.

Accelerated habitual learning resulting from L-dopa exposure in rats is prevented by N-acetylcysteine.

Instrumental actions are initially goal-directed and driven by their associated outcome. However, with repeated experience habitual actions develop which are automated and efficient, as they are instead driven by antecedent stimuli. Dopamine is thought to facilitate the transition from goal-directed to habitual actions.

CO enrichment and soil type additively regulate grassland productivity.

Atmospheric CO enrichment usually increases the aboveground net primary productivity (ANPP) of grassland vegetation, but the magnitude of the ANPP-CO response differs among ecosystems. Soil properties affect ANPP via multiple mechanisms and vary over topographic to geographic gradients, but have received little attention as potential modifiers of the ANPP-CO response. We assessed the effects of three soil types, sandy loam, silty clay and clay, on the ANPP response of perennial C /C grassland communities to a subambient to elevated CO gradient over 10 yr in Texas, USA.

The antihelminthic moxidectin enhances tonic GABA currents in rodent hippocampal pyramidal neurons.

Macrocyclic lactones (MLs) are commonly used treatments for parasitic worm and insect infections in humans, livestock, and companion animals. MLs target the invertebrate glutamate-activated chloride channel that is not present in vertebrates. MLs are not entirely inert in vertebrates, though; they have been reported to have activity in heterologous expression systems consisting of ligand-gated ion channels that are present in the mammalian central nervous system (CNS).

Flowering in grassland predicted by CO and resource effects on species aboveground biomass.

Continuing enrichment of atmospheric CO may change plant community composition, in part by altering the availability of other limiting resources including soil water, nutrients, or light. The combined effects of CO enrichment and altered resource availability on species flowering remain poorly understood. We quantified flowering culm and ramet production and biomass allocation to flowering culms/ramets for 10 years in C -dominated grassland communities on contrasting soils along a CO concentration gradient spanning pre-industrial to expected mid-21st century levels (250-500 μl/L).

Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model.

Cannabinoid pharmacology has proven nettlesome with issues of promiscuity a common theme among both agonists and antagonists. One recourse is to develop allosteric ligands to modulate cannabinoid receptor signaling. Cannabinoids have come late to the allosteric table.

Attenuated sarcomere lengthening of the aged murine left ventricle observed using two-photon fluorescence microscopy.

The Frank-Starling mechanism, whereby increased diastolic filling leads to increased cardiac output, depends on increasing the sarcomere length (Ls) of cardiomyocytes. Ventricular stiffness increases with advancing age, yet it remains unclear how such changes in compliance impact sarcomere dynamics in the intact heart. We developed an isolated murine heart preparation to monitor Ls as a function of left ventricular pressure and tested the hypothesis that sarcomere lengthening in response to ventricular filling is impaired with advanced age.

Dantrolene suppresses spontaneous Ca2+ release without altering excitation-contraction coupling in cardiomyocytes of aged mice.

Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca(2+) homeostasis including altered Ca(2+) cycling through the sarcoplasmic reticulum (SR). The ryanodine receptor antagonist dantrolene exerts antiarrhythmic effects by preventing spontaneous diastolic Ca(2+) release from the SR. We tested the hypothesis that dantrolene prevents spontaneous Ca(2+) release without altering excitation-contraction coupling in aged myocardium.

Genetic manipulation of the cardiac mitochondrial phosphate carrier does not affect permeability transition.

The Mitochondrial Permeability Transition (MPT) pore is a voltage-sensitive unselective channel known to instigate necrotic cell death during cardiac disease. Recent models suggest that the isomerase cyclophilin D (CypD) regulates the MPT pore by binding to either the F0F1-ATP synthase lateral stalk or the mitochondrial phosphate carrier (PiC). Here we confirm that CypD, through its N-terminus, can directly bind PiC.