Chronically elevated levels of glucocorticoids increase food intake, weight gain, and adiposity. Similarly, ghrelin, a gut-secreted hormone, is also associated with weight gain, adiposity, and increased feeding. Here we sought to determine if corticosterone-induced metabolic and behavioral changes require functional ghrelin receptors (GHSR). To do this, we treated male C57BL mice with chronic corticosterone (CORT) mixed in their drinking water for 28 days. Half of these mice received the GHSR antagonist JMV2959 via osmotic minipumps while treated with CORT. In a second experiment, we gave the same CORT protocol to mice with a targeted mutation to the GHSR or their wild-type littermates. As expected, CORT treatment increased food intake, weight gain, and adiposity, but contrary to expectations, mice treated with a GHSR receptor antagonist or GHSR knockout (KO) mice did not show attenuated food intake, weight gain, or adiposity in response to CORT. Similarly, the effects of CORT on the liver were the same or more pronounced in GHSR antagonist-treated and GHSR KO mice. Treatment with JMV2959 did attenuate the effects of chronic CORT on glycemic regulation as determined by the glucose tolerance test. Finally, disruption of GHSR signaling resulted in behavioral responses associated with social withdrawal, potentially due to neuroprotective effects of GHSR activation. In all, we propose that blocking GHSR signaling helps to moderate glucose concentrations when CORT levels are high, but blocking GHSR signaling does not prevent increased food intake, weight gain, or increased adiposity produced by chronic CORT.

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BackgroundThe polytrauma clinical triad (PCT) is a complex disorder composed of three comorbid diagnoses of chronic pain, post-traumatic stress disorder (PTSD), and postconcussion syndrome (PCS). PCT has been documented in veterans returning from deployment, but this is the first report on PCT prevalence in nonmilitary personnel after a motor vehicle collision (MVC).MethodsData were drawn from routine intake assessments completed by 71 patients referred to a community-based clinic for chronic pain management. All patients completed the post-traumatic stress disorder checklist for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (PCL-5), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) during a standardized intake assessment. An additional modified RPQ score was derived to address previously reported symptom overlap between PCS and chronic pain.ResultsStandard and modified RPQ scores yielded PCS prevalence rates of 100% and 54.9% in our sample, respectively. Results suggest that a modified RPQ score, limited to visual and vestibular symptoms, may be more useful PCS screening criteria in patients with chronic pain. PTSD screening criteria on the PCL-5 were met by 85.9% of the patients. More than half of the patients referred for chronic pain after MVC met criteria for PCT (52.1%). Patients who met PCT criteria reported worse headache, overall pain, and sleep quality outcomes.ConclusionAmong patients in our sample with chronic pain after MVC, more than half met criteria for PCT. A modified approach to RPQ scoring limited to visual and vestibular symptoms may be required to screen for PCS in these patients.

Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signalling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signalling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (N=5-8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signalling in female mice.