38 research outputs found

    Cannabinoid CB1 receptor inhibition blunts adolescent-typical increased binge alcohol and sucrose consumption in male C57BL/6J mice

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    Increased binge alcohol consumption has been reported among adolescents as compared to adults in both humans and rodent models, and has been associated with serious long-term health consequences. However, the neurochemical mechanism for age differences in binge drinking between adolescents and adults has not been established. The present study was designed to evaluate the mechanistic role of the cannabinoid CB1 receptor in adolescent and adult binge drinking. Binge consumption was established in adolescent and adult male C57BL/6J mice by providing access to 20% alcohol or 1% sucrose for 4h every other day. Pretreatment with the CB1 antagonist/inverse agonist AM-251 (0, 1, 3, and 10mg/kg) in a Latin square design dose-dependently reduced adolescent alcohol consumption to adult levels without altering adult intake. AM-251 (3mg/kg) also reduced adolescent but not adult sucrose consumption. Adolescent reductions in alcohol and sucrose were not associated with alterations in open-field locomotor activity or thigmotaxis. These findings point to age differences in CB1 receptor activity as a functional mediator of adolescent-typical increased binge drinking as compared to adults. Developmental alterations in endocannabinoid signaling in the adolescent brain may therefore be responsible for the drinking phenotype seen in this age group

    Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice

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    Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction

    SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

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    Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

    Socioeconomic analysis of environmental concern: Case of the Four Corners electric power complex

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    Introduction; Cultural and economic characteristics of the region; Population and geography; Tourism and recreation; Mining; Power generation; Previous studies-attitudes toward pollution; Hypotheses; Sample; Bidding games; Results; Concern for environment; Who should pay; Residents; Recreationists; Reservation residents; Compensation games; Conclusions; On hypotheses; On bidding games; Implications and applications; Literature cited; AppendixBulletin containing an analysis of socioeconomic characteristics of the electric power industry correlated with concern for environmental quality based on consumers' willingness to pay for environmental cleanup

    New Mexico small farms: A socio-economic profile

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    Introduction; New Mexico's principal agricultural regions; Sources of data; Family farms and small farms; Cultural antecedents of the family farm; Small farm: a working definition; Structure of New Mexico agriculture; Gross agriculture sales and farm debt; Farm acreage; Off-farm income and employment; Residence, tenure and age; Situation and goals; Conclusions and implications; Conclusions; Implications for agricultural policy, extension and research; References citedResearch report containing the results of a study to gather basic socioeconomic data on small farms in New Mexico in order to assist with future research, governmental assistance, and extension programming

    Impact of increasing wages on New Mexico chile production

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    Background; Data and analysis; Minimum wage; Imports from Mexico; Costs and returns of chile production; Discussion and conclusions; ReferencesResearch report containing the results of a study to determine the effect of rising minimum wages on chile production practices in southern New Mexico

    Attitudes toward energy use and policy in New Mexico

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    Acknowledgments; The survey; Perceptions and preferences; Seriousness of situation; Some cuases of shortage; Whom to believe; National security and pollution; A look ahead; Consumer products; Conservation policies; Comparisons with other studies; Conclusions and observations; Bibliography; Appendix A; Appendix BResearch report containing the results of a survey to determine the perceptions and attitudes about energy issues among New Mexicans in the late 1970s
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