This study was designed to assess the relative influence of meal weight and caloric content on gastric emptying of liquid and solid meals in man. A dual radioisotopic method which permits noninvasive and simultaneous measurement of liquid- and solid-phase emptying by external gamma camera techniques was employed. Nine healthy volunteer subjects ingested 50-, 300-, and 900-g lettuce and water meals adjusted to either 68, 208, or 633 kcal with added salad oil. The following observations were made: (1) absolute emptying rates (grams of solid food emptied from the stomach per minute) increased directly and significantly with meal weight; (2) increasing meal total caloric content significantly slowed solid food gastric emptying but did not overcome the enhancing effect of meal weight; and (3) liquid emptying rates were uninfluenced by meal total kcal amount.

Background The effects of stress, including neuroendocrine and behavioral sequelae aimed at maintaining homeostasis, are associated with increased alcohol consumption. Because both stress and drinking are multifactorial, the mechanisms underlying the relationship are difficult to elucidate. We therefore employed an animal model investigating the influence of blocked access to a running wheel on drinking in C57BL/6J (B6) mice. Methods In the first experiment, naïve, adult male and female subjects were individually housed for 2 weeks with 24hr access to a running wheel and 12% EtOH in a 2-bottle, free choice paradigm. After determining baseline consumption and preference, experimental subjects had the running wheel placed in a locked position for 6hr, and the EtOH bottle was removed during the first half of this period. Two subsequent experiments, again in adult, naïve B6 mice, examined the influence of locked running wheels on self-administration of 20% EtOH in a limited access paradigm, and blood EtOH concentrations (BECs) were determined. Results In all three studies, using both between and within subject analyses, females showed transient yet reliable increases in alcohol drinking during blocked access to a rotating activity, while drinking in male mice was largely insensitive to this manipulation, though both sexes showed appreciable BECs (>130 mg/dL in females, and 80 mg/dL in males) following a 2hr EtOH access period. Conclusions These data add to a burgeoning literature suggesting that the factors contributing to excessive alcohol use differ between males and females, and that females may be especially sensitive to the influence of wheel manipulation. Elucidating the sex-dependent mechanisms mediating differences in alcohol sensitivity and response is critical to understanding the causes of alcoholism and in developing effective treatments and interventions.

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Background: Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD. Methods: Rats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4% w/w, 5 weeks) vs. un-supplemented diet, and impact on depression-like behavior, brain bioenergetics, serotonin and SSRI efficacy assessed. Results: CRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone. Conclusions: Dietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin.