Neuronal Activity Within the Ventral Tegmental Area Is Correlated with Cocaine-Seeking Behavior in Male, But Not Female, Rats

The objective of this study was to begin to determine the neurobiological underpinnings of psychosocial stress-induced cocaine seeking. Social defeat stress, achieved using the well-established resident-intruder procedure, is an ecologically-valid psychosocial stressor in rodents that may more closely recapitulate those psychosocial experiences that elicit cocaine craving and relapse in human cocaine users. Our laboratory has developed a model of psychosocial stress-induced relapse in rats in which extinguished cocaine seeking is reinstated by re-exposure to a discrete cue that signals impending social defeat stress. We previously reported that an individual rat’s predilection towards the display of active coping behaviors during prior social defeat stress exposures was positively correlated with levels of psychosocial stress-induced cocaine seeking. The current study’s goal was to expand upon these initial findings by assessing and comparing patterns of neural activation within the ventral tegmental area (VTA) during stress-induced cocaine seeking triggered by psychosocial stress-predictive or foot shock stress-predictive cues. The VTA was selected for investigation in the present study because of its known role in the manifestation of stress-induced reinstatement of cocaine seeking. We postulated that neural activation in this brain region would be associated with the magnitude of observed psychosocial stress-induced cocaine seeking, thus providing important insights into the neurobiological underpinnings of this phenomenon

Effects of Sex and Estrous Cycle on Intravenous Oxycodone Self-Administration and the Reinstatement of Oxycodone-Seeking Behavior in Rats

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a fixed-ratio 1 schedule of reinforcement in daily 2-hr sessions, and a dose-response function was subsequently determined (0.003-0.03 mg/kg/inf). In experiment 2, a separate group of adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone for 8 sessions, followed by 0.01 mg/kg/inf oxycodone for 10 sessions. Responding was then extinguished, followed by sequential footshock-induced and cue-induced reinstatement tests. In the dose-response experiment, oxycodone produced a typical inverted U-shape function with 0.01 mg/kg/inf representing the maximally effective dose in both sexes. No sex differences were detected in the reinforcing efficacy of oxycodone. In the second experiment, the reinforcing effects of 0.01-0.03 mg//kg/inf oxycodone were significantly attenuated in females during proestrus/estrus as compared to metestrus/diestrus phases of the estrous cycle. Neither males nor females displayed significant footshock-induced reinstatement of oxycodone seeking, but both sexes exhibited significant cue-induced reinstatement of oxycodone seeking at magnitudes that did not differ either by sex or by estrous cycle phase. These results confirm and extend previous work suggesting that sex does not robustly influence the primary reinforcing effects of oxycodone nor the reinstatement of oxycodone-seeking behavior. However, our findings reveal for the first time that the reinforcing efficacy of IV oxycodone varies across the estrous cycle in female rats

Quantum Sensing for Detection of Zinc-Triggered Free Radicals in Endothelial Cells

Oxidative stress originating from the overproduction of free radicals poses a major threat to cell fate, therefore it is of great importance to address the formation of free radicals in cells subjected to various pathological stimuli. Here we investigate the free radical response of endothelial cells to biodegradable zinc. In addition to the standard free radical assays, relaxometry was used for determining the production of free radicals in cells exposed to non-physiological concentrations of zinc ions. The cellular morphology, intracellular zinc accumulation, as well as the levels of reactive oxygen/nitrogen species, are determined using standard fluorescent methods. For endothelial cells subjected to 50% zinc extracts, deviations from the normal cell shape and cell agglomeration tendency are observed. The culture medium containing the highest amount of zinc ions caused nuclei fragmentation, blebbing, and cell shrinkage, indicating cell death. A potential explanation for the observed phenomena is an overproduction of free radicals. In the case of 1% and 10% zinc extracts, the formation of free radicals is clearly confirmed by relaxometry, while the results obtained by using fluorescent techniques are unambiguous. It is revealed that high concentrations of zinc ions released from biodegradable samples induce a deleterious effect on endothelial cells.</p

Quantum Sensing for Detection of Zinc-Triggered Free Radicals in Endothelial Cells

Oxidative stress originating from the overproduction of free radicals poses a major threat to cell fate, therefore it is of great importance to address the formation of free radicals in cells subjected to various pathological stimuli. Here we investigate the free radical response of endothelial cells to biodegradable zinc. In addition to the standard free radical assays, relaxometry was used for determining the production of free radicals in cells exposed to non-physiological concentrations of zinc ions. The cellular morphology, intracellular zinc accumulation, as well as the levels of reactive oxygen/nitrogen species, are determined using standard fluorescent methods. For endothelial cells subjected to 50% zinc extracts, deviations from the normal cell shape and cell agglomeration tendency are observed. The culture medium containing the highest amount of zinc ions caused nuclei fragmentation, blebbing, and cell shrinkage, indicating cell death. A potential explanation for the observed phenomena is an overproduction of free radicals. In the case of 1% and 10% zinc extracts, the formation of free radicals is clearly confirmed by relaxometry, while the results obtained by using fluorescent techniques are unambiguous. It is revealed that high concentrations of zinc ions released from biodegradable samples induce a deleterious effect on endothelial cells.</p

Texture-Governed Cell Response to Severely Deformed Titanium

The phenomenon of superior biological behavior , r it observed in titanium processed by an unconventional severe plastic deformation method, that is, hydrostatic extrusion, has been described within the present study. In doing so, specimens varying significantly in the crystallographic orientation of grains, yet exhibiting comparable grain refinement, were meticulously investigated. The aim was to find the clear origin of enhanced biocompatibility of titanium-based materials, having microstructures scaled down to the submicron range. Texture, microstructure, and surface characteristics, that is, wettability, roughness, and chemical composition, were examined as well as protein adsorption tests and cell response studies were carried out. It has been concluded that, irrespective of surface properties and mean grain size, the (10 (1) over bar0) crystallographic plane favors endothelial cell attachment on the surface of the severely deformed titanium. Interestingly, an enhanced albumin, fibronectin, and serum adsorption as well as dearly directional growth of the cells with preferentially oriented cell nuclei have been observed on the surfaces having (0001) planes exposed predominantly. Overall, the biological response of titanium fabricated by severe plastic deformation techniques is derived from the synergistic effect of surface irregularities, being the effect of refined microstructures, surface chemistry, and crystallographic orientation of grains rather than grain refinement itself

Neuroactivational and Behavioral Correlates of Psychosocial Stress-Induced Cocaine Seeking in Rats

A prominent feature of cocaine abuse is a high risk of relapse even despite prolonged periods of abstinence. Psychosocial stress is thought to be a major contributor to the onset of cocaine craving and relapse in human substance abusers, yet most preclinical models of stress-induced relapse employ physical stressors (e.g., unpredictable footshock) or pharmacological stressors (e.g., yohimbine to elicit a drug seeking response) and do not rely upon psychosocial stress per se. Importantly, social stressors are well known to activate distinct neural circuits within the brain as compared to other stressors. It is therefore possible that currently available animal models of stress-induced drug relapse do not fully engage the neuroanatomical, neurochemical, and/or molecular substrates that are recruited specifically by psychosocial stressors to produce drug-seeking behavior. Social defeat stress has been proposed as an ethologically valid psychosocial stressor in rodents that more closely models the forms of psychosocial stress that precede relapse episodes in drug abusers. We previously developed a model of psychosocial stress-induced reinstatement in rats in which cocaine seeking is elicited via exposure to a cue signaling impending social defeat stress. Using this model, we discovered that predilection towards displaying active coping behaviors during prior social defeat stress exposures was positively correlated with levels of psychosocial stress-induced cocaine seeking. The present study aimed to expand upon these initial findings by assessing and comparing patterns of neural activation in key brain areas during stress induced cocaine seeking that is triggered by psychosocial or footshock stress predictive cues

Evaluating Health Research Capacity Building: An Evidence-Based Tool

Bates and colleagues describe the development of a tool to assess capacity-building programs in health research, which they used in Kumasi, Ghana

Quantum Sensing for Detection of Zinc-Triggered Free Radicals in Endothelial Cells

Oxidative stress originating from the overproduction of free radicals poses a major threat to cell fate, therefore it is of great importance to address the formation of free radicals in cells subjected to various pathological stimuli. Here we investigate the free radical response of endothelial cells to biodegradable zinc. In addition to the standard free radical assays, relaxometry was used for determining the production of free radicals in cells exposed to non-physiological concentrations of zinc ions. The cellular morphology, intracellular zinc accumulation, as well as the levels of reactive oxygen/nitrogen species, are determined using standard fluorescent methods. For endothelial cells subjected to 50% zinc extracts, deviations from the normal cell shape and cell agglomeration tendency are observed. The culture medium containing the highest amount of zinc ions caused nuclei fragmentation, blebbing, and cell shrinkage, indicating cell death. A potential explanation for the observed phenomena is an overproduction of free radicals. In the case of 1% and 10% zinc extracts, the formation of free radicals is clearly confirmed by relaxometry, while the results obtained by using fluorescent techniques are unambiguous. It is revealed that high concentrations of zinc ions released from biodegradable samples induce a deleterious effect on endothelial cells.</p

Microstructure-properties relation of hydrostatically extruded absorbable zinc alloys:Effect of Mg and Cu addition on corrosion properties and biocompatibility

Pure Zn is well-known for its appropriate corrosion rate, making it suitable for use as future absorbable implants. Yet, it suffers from insufficient strength, thus, both plastic deformation and alloying are required. Hydrostatic extrusion has proven to be an efficient technique, providing high mechanical properties for zinc alloys. However, its effect on degradation rate and biocompatibility of Zn alloys remains unknown. Thus, within the present study, an attempt to evaluate those properties has been made on hydrostatically extruded pure Zn, Zn–Mg and Zn–Mg–Cu alloys. The materials were characterized by advanced microscopy techniques and uniaxial tensile tests. Corrosion properties were assessed based on electrochemical and static immersion tests. Finally, the cytotoxic effect of zinc extracts on endothelial cells were examined by standard MTT assays combined with confocal imaging. The results showed that hydrostatic extrusion results in significant refinement of α-Zn grains and the intermetallic phase Mg2Zn11 for the investigated alloys. The alloys exhibited ultimate tensile strength exceeding 300 MPa and elongation higher than 20%. Corrosion tests demonstrated that all the materials showed a similar level of degradation rate. Moreover, the uniform distribution of the intermetallic phase contributed to homogeneous corrosion of Zn alloys. Biological studies indicated that the least cytotoxic response in endothelial cells was obtained for the Zn–Mg alloy. Such an effect was caused by the limited amount of released Zn ions in the favor of Mg ions. The refinement of α-Zn grains and intermetallic phases caused by hydrostatic extrusion were key factors determining the performance of Zn-based materials.</p

Determining the Conformational Landscape of σ and π Coupling Using <i>para</i>-Phenylene and “Aviram–Ratner” Bridges

The torsional dependence of donor–bridge–acceptor (D–B–A) electronic coupling matrix elements (<i><b>H</b></i>_{<i><b>DA</b></i>}, determined from the magnetic exchange coupling, <i><b>J</b></i>) involving a spin S_D = 1/2 metal semiquinone (Zn-<b>SQ</b>) donor and a spin S_A = 1/2 nitronylnitroxide (<b>NN</b>) acceptor mediated by the σ/π-systems of <i>para</i>-phenylene and methyl-substituted <i>para</i>-phenylene bridges and by the σ-system of a bicyclo[2.2.2]­octane (<b>BCO</b>) bridge are presented and discussed. The positions of methyl group(s) on the phenylene bridge allow for an experimentally determined evaluation of conformationally dependent (π) and conformationally independent (σ) contributions to the electronic and magnetic exchange couplings in these D–B–A biradicals at parity of D and A. The trend in the experimental magnetic exchange couplings are well described by CASSCF calculations. The torsional dependence of the pairwise exchange interactions are further illuminated in three-dimensional, “Ramachandran-type” plots that relate D–B and B–A torsions to both electronic and exchange couplings. Analysis of the magnetic data shows large variations in magnetic exchange (<i><b>J</b></i> ≈ 1–175 cm^–1) and electronic coupling (<i><b>H</b></i>_{<i><b>DA</b></i>} ≈ 450–6000 cm^–1) as a function of bridge conformation relative to the donor and acceptor. This has allowed for an experimental determination of both the σ- and π-orbital contributions to the exchange and electronic couplings