Are Protective Labor Market Institutions Really at the Root of Unemployment? A Critical Perspective on the Statistical Evidence

This report debunks the myth that labor market protections, such as unions and unemployment benefits, are responsible for high European unemployment rates.

ECONOMICALLY OPTIMAL NITROGEN FERTILIZATION FOR YIELD AND PROTEIN IN HARD RED SPRING WHEAT

This analysis determines profit maximizing N fertilization levels of hard red spring wheat (HRSW) for various wheat prices, N prices, and protein-based HRSW price premium/discount (P/D) structures for south eastern Washington data. Fertilizer response data consisting of rates of N fertilization (lb/ac), grain yield (bu/ac), and grain protein (%) were used to statistically estimate regression relationships that predicted yield and protein in response to N. All predicted net return maximizing N, protein, and yield levels were within the data range. Increasing P/D incentives for protein increased optimal N, the expected economic result. At the high P/D structures, the P/D structure dominated N and wheat prices in determining optimal N application levels. Overall, net return-maximizing yields varied only modestly with changes in both N and wheat price in this data set. However, in all scenarios, as P/D incentives increased, net return maximizing N levels were beyond the level that resulted in maximum yield. At the two lowest P/D structures, which provided the lowest reward for protein, it was most profitable to fertilize for slightly less than 14% expected protein. These results indicate that it is not always profitable to use 14% protein as an N fertilization goal. Abbreviations: CT, conventional tillage; HRSW, hard red spring wheat; HRWW, hard red winter wheat; N, nitrogen; NO3, nitrate; NT, No Tillage; P/D, premium/discount; SWSW, soft white spring wheat; SWW, soft white wheat.Crop Production/Industries,

Stress-Induced Cocaine Seeking Requires a Beta-2 Adrenergic Receptor-Regulated Pathway from the Ventral Bed Nucleus of the Stria Terminalis That Regulates CRF Actions in the Ventral Tegmental Area

The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses β adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the β-2 AR antagonist, ICI-118,551, but not the β-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of the β-2 AR agonist, clenbuterol, but not the β-1 agonist, dobutamine, reinstated cocaine seeking, suggesting that activation of vBNST β-2 AR is both necessary for stress-induced reinstatement and sufficient to induce cocaine seeking. The contribution of a β-2 AR-regulated vBNST-to-VTA pathway that releases CRF was investigated using a disconnection approach. Injection of ICI-118,551 into the vBNST in one hemisphere and antalarmin into the VTA of the contralateral hemisphere prevented footshock-induced reinstatement, whereas ipsilateral manipulations failed to attenuate stress-induced cocaine seeking, suggesting that β-2 AR regulate vBNST efferents that release CRF into the VTA, activating CRF receptors, and promoting cocaine use. Last, reinstatement by clenbuterol delivered bilaterally into the vBNST was prevented by bilateral vBNST pretreatment with antalarmin, indicating that β-2 AR-mediated actions in the vBNST also require local CRF receptor activation. Understanding the processes through which stress induces cocaine seeking should guide the development of new treatments for addiction

Low-Voltage Bandgap Reference Design Utilizing Schottky Diodes

As semiconductor device geometries continue to shrink, the corresponding voltage applied across the processed devices must also be reduced. Therefore reference voltages used in integrated circuits will need to be reduced as well. A typical bandgap reference (BGR) voltage generator uses PN junction diodes or PNP BJT’s to bias the reference. The forward bias voltage of these devices is typically 0.7 volts, and has a limiting effect on how low a reference voltage can be generated, as well as how low a system voltage can be applied. Schottky, or metal-semiconductor (MS), diodes have a lower forward bias voltage, typically of about 0.3 volts. The implementation of Schottky metal-semiconductor diodes in place of PN diodes in the design of the BGR, should allow for lower reference voltage generation. This project consists of the design and simulation of a BGR utilizing MS diodes, followed by fabrication and validation of the design

Drug-Induced Plasticity Contributing to Heightened Relapse Susceptibility: Neurochemical Changes and Augmented Reinstatement in High-Intake Rats

A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for cocaine-induced reinstatement. In this report, we examined whether drug-induced adaptations that are necessary to generate cocaine-induced reinstatement also determine relapse vulnerability. To do this, rats were assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5 mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug intake since these manipulations produce groups of rats exhibiting differences in the magnitude of cocaine-induced reinstatement. Approximately 19 d after the last session, cocaine-induced drug seeking and extracellular levels of glutamate and dopamine in the NAcc were measured. Contrary to our hypothesis, high-intake rats exhibited a more robust cocaine-induced increase in extracellular levels of dopamine but not glutamate. Further, increased reinstatement in high-intake rats was no longer observed when the D1 receptor antagonist SCH-23390 was infused into the NAcc. The sensitized dopamine response to cocaine in high-intake rats may involve blunted cystine–glutamate exchange by system xc−. Reduced 14C-cystine uptake through system xc− was evident in NAcc tissue slices obtained from high-intake rats, and the augmented dopamine response in these rats was no longer observed when subjects received the cysteine prodrug N-acetyl cysteine. These data reveal a role for drug-induced NAcc dopamine in heightened relapse vulnerability observed in rats with a history of high levels of drug intake

Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats

Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1.0 mg/kg/ing; 14 × 6 h/day) and extinction and were tested for reinstatement in response to footshock (0.5 mA, 0.5” duration, average every 40 s; range 10–70 s) or intra-VTA CRF delivery (500 ng/side) following intra-VTA pretreatment with the GABA-A antagonist, bicuculline, the GABA-B antagonist, 2-hydroxysaclofen or vehicle. Intra-VTA bicuculline (1, 10 or 20 ng/side) failed to block footshock- or CRF-induced cocaine seeking at either dose tested. By contrast, 2-hydroxysaclofen (0.2 or 2 μg/side) prevented reinstatement by both footshock and intra-VTA CRF at a concentration that failed to attenuate food-reinforced lever pressing (45 mg sucrose-sweetened pellets; FR4 schedule) in a separate group of rats. These data suggest that GABA-B receptor-dependent CRF actions in the VTA mediate stress-induced cocaine seeking and that GABA-B receptor antagonists may have utility for the management of stress-induced relapse in cocaine addicts

Blunted Cystine–Glutamate Antiporter Function in the Nucleus Accumbens Promotes Cocaine-induced Drug Seeking

Repeated cocaine alters glutamate neurotransmission, in part, by reducing cystine–glutamate exchange via system xc−, which maintains glutamate levels and receptor stimulation in the extrasynaptic compartment. In the present study, we undertook two approaches to determine the significance of plasticity involving system xc−. First, we examined whether the cysteine prodrug N-acetylcysteine attenuates cocaine-primed reinstatement by targeting system xc−. Rats were trained to self-administer cocaine (1 mg/kg/200 μl, i.v.) under extended access conditions (6 h/day). After extinction training, cocaine (10 mg/kg, i.p.) primed reinstatement was assessed in rats pretreated with N-acetylcysteine (0–60 mg/kg, i.p.) in the presence or absence of the system xc− inhibitor (S)-4-carboxyphenylglycine (CPG; 0.5 μM; infused into the nucleus accumbens). N-acetylcysteine attenuated cocaine-primed reinstatement, and this effect was reversed by co-administration of CPG. Secondly, we examined whether reduced system xc− activity is necessary for cocaine-primed reinstatement. To do this, we administered N-acetylcysteine (0 or 90 mg/kg, i.p.) prior to 12 daily self-administration sessions (1 mg/kg/200 μl, i.v.; 6 h/day) since this procedure has previously been shown to prevent reduced activity of system xc−. On the reinstatement test day, we then acutely impaired system xc− in some of the rats by infusing CPG (0.5 μM) into the nucleus accumbens. Rats that had received N-acetylcysteine prior to daily self-administration sessions exhibited diminished cocaine-primed reinstatement; this effect was reversed by infusing the cystine–glutamate exchange inhibitor CPG into the nucleus accumbens. Collectively these data establish system xc− in the nucleus accumbens as a key mechanism contributing to cocaine-primed reinstatement

CB1 Receptor Antagonism Blocks Stress-Potentiated Reinstatement of Cocaine Seeking in Rats

Rationale Under some conditions, stress, rather than directly triggering cocaine seeking, potentiates reinstatement to other stimuli, including a subthreshold cocaine dose. The mechanisms responsible for stress-potentiated reinstatement are not well defined. Endocannabinoid signaling is increased by stress and regulates synaptic transmission in brain regions implicated in motivated behavior. Objectives The objective of this study was to test the hypothesis that cannabinoid type 1 receptor (CB1R) signaling is required for stress-potentiated reinstatement of cocaine seeking in rats. Methods Following i.v. cocaine self-administration (2 h access/day) and extinction in male rats, footshock stress alone does not reinstate cocaine seeking but reinstatement is observed when footshock is followed by an injection of an otherwise subthreshold dose of cocaine (2.5 mg/kg, i.p.). CB1R involvement was tested by systemic administration of the CB1R antagonist AM251 (0, 1, or 3 mg/kg, i.p.) prior to testing for stress-potentiated reinstatement. Results Stress-potentiated reinstatement was blocked by both 1 and 3 mg/kg AM251. By contrast, AM251 only attenuated food-reinforced lever pressing at the higher dose (i.e., 3 mg/kg) and did not affect locomotor activity at either dose tested. Neither high-dose cocaine-primed reinstatement (10 mg/kg, i.p.) nor footshock stress-triggered reinstatement following long-access cocaine self-administration (6 h access/day) was affected by AM251 pretreatment. Footshock stress increased concentrations of both endocannabinoids, N-arachidonylethanolamine and 2-arachidonoylglycerol, in regions of the prefrontal cortex. Conclusions These findings demonstrate that footshock stress increases prefrontal cortical endocannabinoids and stress-potentiated reinstatement is CB1R-dependent, suggesting that CB1R is a potential therapeutic target for relapse prevention, particularly in individuals whose cocaine use is stress-related