Recent social influence research utilizing psychological reactance theory (J. W. Brehm, 1966) has focused on how reactance motivates message rejection due to threats to perceived freedoms posed by controlling language. Although reactance has been shown to increase message rejection and source derogation, persuasive appeals employing alternative forms of restoration of freedom, as suggested by the theory, have received little if any empirical scrutiny. The present study manipulated the levels of controlling language and lexical concreteness within health messages targeting a young adult population. Results show a number of negative outcomes associated with the use of controlling language but suggest more positive outcomes associated with the use of restoration postscripts. Findings also indicate that relative to abstract language, messages using concrete language receive more attention, are viewed as more important, and generate more positive assessments of the source.

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.

Taken together, these data suggest that magnitude of antinociceptive tolerance is inversely related to relative efficacy of mu agonists, with lower efficacy agonists being more susceptible to tolerance than are higher efficacy agonists under these intermittent dosing conditions.

No disease-modifying therapies are currently available for Alzheimer's disease (AD), a neurodegenerative disorder that affects more than 36 million people worldwide. Although cardiovascular risk factors such as hypertension and diabetes are increasingly implicated as contributing to the development of AD, the mechanisms whereby these factors influence pathological processes in the AD brain have not been defined. Here we propose, for the first time, vascular activation as a relevant mechanism in AD pathogenesis. We explore this hypothesis in two transgenic AD animal models: AD2576APPSwe (AD2576) and LaFerla 3xTg (3xTgAD) mice using the vascular activation inhibitor sunitinib. Our data show that in both AD animal models, the cerebrovasculature is activated and overexpresses amyloid beta, thrombin, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and matrix metalloproteinase 9. Oral administration of sunitinib significantly reduces vascular expression of these proteins. Furthermore, sunitinib improves cognitive function, as assessed by several behavioral paradigms, in both AD animal models. Finally, oxidant injury of brain endothelial cells in culture, resulting in expression of inflammatory proteins, is mitigated by sunitinib. The current data, as well as published studies showing cerebrovascular activation in human AD, support further exploration of vascular-based mechanisms in AD pathogenesis. New thinking about AD pathogenesis and novel, effective treatments are urgently needed. Identification of "vascular activation" as a heretofore unexplored target could stimulate translational investigations in this newly defined area, leading to innovative therapeutic approaches for the treatment of this devastating disease.

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Rats responded under a schedule in which every 30th lever press (fixed ratio 30) produced a food pellet during sessions divided into six 5-min ratio components separated by 10-min timeout (TO) periods. Cumulative doses of morphine or naloxone were administered at the start of consecutive TO periods. When given alone, morphine decreased response rates in a dose-dependent manner, abolishing responding at 10 or 17.8 mg/kg. Naloxone doses of 0.1 and 1.0 mg/kg restored rates and patterns of behavior suppressed by a dose of 17.8 mg/kg morphine; doses of 0.32 to 10 mg/kg prevented the rate-decreasing effects of cumulative morphine doses. When administered alone, naloxone initially decreased response rates at a cumulative dose of 32 to 100 mg/kg; with repeated testing and intervening morphine exposure, the required cumulative dose was decreased to 10 or 32 mg/kg. An acute 10 mg/kg morphine pretreatment, given 4 h before the session, decreased the cumulative naloxone dose required to suppress rates an additional 10- to 30-fold. This effect was time-dependent and dose-dependent, and the usual naloxone dose-response function could be recaptured 1 week after the pretreatment effect was obtained. In contrast, acute morphine pretreatment did not alter either the cumulative dose of morphine itself required to suppress rates or the naloxone dose required to reverse or prevent morphine's rate-decreasing effects.

Cardiovascular risk factors, such as oxidative stress and elevated lipids, are linked to the development of cognitive impairment. A mediator common to both stressors is the apolipoprotein E (apoE). The objectives of this study are to determine the effects of apoE deficiency and diet-induced systemic oxidative stress in mice on vascular expression of inflammatory proteins and on cognitive function. Mice are placed on a diet enriched in homocysteine for fifteen weeks and then assessed for spatial learning using an eight-arm radial maze and for inflammatory protein expression by immunohistochemistry. Our results show that diet-induced oxidative stress does not affect cognitive function in normal mice. In contrast, apoE−/− mice on the homocysteine diet show significantly impaired (p < 0. 001) maze performance. ApoE−/− mice also have high cholesterol levels. There is no expression of inflammatory proteins IL-6 and IL-8 in the vasculature of control mice on normal or homocysteine diet and little in apoE−/− mice on normal diet. In contrast, apoE−/− mice on homocysteine diet show pronounced vascular reactivity to IL-6 and IL-8 antibodies. These data show that systemic oxidative stress correlates with expression of inflammatory proteins in the cerebral vasculature and impaired cognitive function. These results are consistent with the hypothesis that an oxidative-inflammatory cycle in the cerebral vasculature could have deleterious consequences for cognition.

Morphine-amphetamine and morphine-naltrexone interactions were examined in three groups of White Carneaux pigeons (n = 3), which were trained in a two-choice drug discrimination procedure under a FR-30 schedule of food reinforcement using 3.2 mg/kg morphine and saline as discriminative stimuli. Once stimulus control was acquired by these initial training stimuli, the training doses of morphine were gradually changed to 1.0 mg/kg for group A and to 10 mg/kg for group C. The three groups differed in the minimum dose required for stimulus control and the drugs to which the training stimulus generalized. Stimulus generalization to amphetamine was inversely related to training dose. Amphetamine potentiated the discriminative stimulus properties of morphine. Naltrexone blocked the discriminative stimulus properties of morphine to varying degrees, which appeared to be limited by the training dose and the rate-suppressing effects of naltrexone when administered alone. Challenging the morphine stimulus with amphetamine resulted in a qualitatively similar blockade. This blockade was a direct function of the morphine training dose. It is argued that MS-AMP interactions result in perceptual masking of the MS stimulus, which can be differentiated from pharmacological antagonism by NTX. Two other challenge drugs, ketamine and sodium pentobarbital, did not alter stimulus control by morphine.