[1] This paper presents a weather generator that allows simulation of hydrometeorological variables representative of a given geographic location: precipitation, total cloud cover, incoming shortwave radiation, air temperature, humidity, and wind speed. The approach captures the essential relationships among the quantities of interest, while modeling the diurnal variation of weather conditions at the hourly scale. Precipitation is considered to be the key driver of simulated hydrometeorological conditions, which leads to a consistent covariation of the weather variables. The generator was calibrated and validated with data from three meteorological stations located in New Mexico, Arizona, and Oklahoma. The set of variables reproduced by the weather generator can serve as input to a number of models of environmental systems, involving hydrological, ecological, water resources, and agricultural applications. The model is also suitable for creating scenarios of climate regimes (e.g., dry versus wet climates) useful in sensitivity studies. The source codes of the weather generator, manual, and test applications are publicly available.

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Background New pharmacotherapies to treat Alcohol Use Disorders (AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol drinking in mice. To test the hypothesis that suppression of high ethanol consumption is a general property of tetracyclines, we screened several derivatives for anti-drinking activity using the Drinking-In-the-Dark (DID) paradigm. Active drugs were studied further using the dose-response relationship. Methods Adult female and male C57BL/6J mice were singly housed and the DID paradigm was performed using 20% ethanol over a 4-day period. Mice were administered a tetracycline or its vehicle 20 h prior to drinking. Water and ethanol consumption was measured daily. Body weight was measured at the start of drug injections and after the final day of the experiment. Blood was collected for ethanol content measurement immediately following the final bout of drinking. Results Seven tetracyclines were tested at a 50 mg/kg dose. Only minocycline and tigecycline significantly reduced ethanol drinking, and doxycycline showed a strong effect-size trend towards reduced drinking. Subsequent studies with these three drugs revealed a dose-dependent decrease in ethanol consumption for both female and male mice, with sex differences in efficacy. Minocycline and doxycycline reduced water intake at higher doses, although to a lesser degree than their effects on ethanol drinking. Tigecycline did not negatively affect water intake. The rank order of potency for reduction in ethanol consumption was minocycline > doxycycline > tigecycline, indicating efficacy was not strictly related to their partition-coefficients (LogP) or distribution constants (LogD). Conclusions Due to its effectiveness in reducing high ethanol consumption coupled without an effect on water intake, tigecycline was found to be the most promising lead tetracycline compound for further study toward the development of a new pharmacotherapy for the treatment of AUD.

BackgroundPhysicians have long reported that patients with chronic pain show higher tendencies for alcohol use disorder (AUD), and AUD patients appear to have higher pain sensitivities. The goal of this study was to test 2 hypotheses: (i) binge alcohol consumption increases inflammatory pain and mechanical and cold sensitivities; and (ii) tigecycline is an effective treatment for alcohol‐mediated‐increased pain behaviors and sensitivities. Both female and male mice were used to test the additional hypothesis that important sex differences in the ethanol (EtOH)‐related traits would be seen.Methods“Drinking in the Dark” (DID) alcohol consuming and nondrinking control, female and male, adult C57BL/6J mice were evaluated for inflammatory pain behaviors and for the presence of mechanical and cold sensitivities. Inflammatory pain was produced by intraplantar injection of formalin (10 μl, 2.5% in saline). For cold sensation, a 20 μl acetone drop was used. Mechanical withdrawal threshold was measured by an electronic von Frey anesthesiometer. Efficacy of tigecycline (80 mg/kg i.p.) to reduce DID‐related pain responses and sensitivity was tested.Results DID EtOH consumption increased inflammatory pain behavior, while it also produced sustained mechanical and cold sensitivities in both females and males. Tigecycline produced antinociceptive effects in males; a pro‐nociceptive effect was seen in females in the formalin test. Likewise, the drug reduced both mechanical and cold sensitivities in males, but females showed an increase in sensitivity in both tests.ConclusionsOur results demonstrated that binge drinking increases pain, touch, and thermal sensations in both sexes. In addition, we have identified sex‐specific effects of tigecycline on inflammatory pain, as well as mechanical and cold sensitivities. The development of tigecycline as an AUD pharmacotherapy may need consideration of its pro‐nociceptive action in females. Further studies are needed to investigate the mechanism underlying the sex‐specific differences in nociception.