Exploring mental health approaches and curriculum in physiotherapy: an Australasian perspective.

BACKGROUND: Exposure to mental health problems are becoming increasingly more frequent within physiotherapy. Physiotherapists recognize the need for a biopsychosocial approach, however their knowledge, assessment, and treatment skills specific to mental health problems requires further research. PURPOSE: To profile the level of education and perception of education that physiotherapists have acquired specific to mental health problems; and to profile an understanding of the current practice of physiotherapists specific to mental health problems. METHODS: An online survey addressed the aims of the study and collected data from physiotherapists in Australia and New Zealand (open between 20th of October 2022 to the 20th of March 2023). RESULTS: 139 respondents were included in the analysis. Physiotherapists had a perception that a significantly greater amount of coursework related to mental health needed to be included within their initial degree compared to what they received (mean difference of 20.0%, 95% CI: 17.5 to 22.5). This trend was evident irrespective of the degree level or the year of graduation. Higher perceived knowledge of anxiety (MD of 11.4, p = 0.001, ES: 0.5) and depression (MD of 11.8, p = 0.001, ES: 0.5) was evident in outpatient care physiotherapists. Lack of perceived knowledge is a reason for whether an assessment or treatment strategy is used with patients experiencing a mental health problem. Motivational interviewing and mindfulness were the most frequently used psychologically based techniques. CONCLUSION: This study reveals the need to increase the amount of mental health and psychologically based techniques within Physiotherapy curriculum.

Heat stress of gilts around farrowing causes oxygen insufficiency in the umbilical cord and reduces piglet survival.

Late gestating sows are susceptible to high ambient temperatures, possibly causing farrowing complications and reducing piglet survival. This experiment aimed to quantify in the days leading up to farrowing the impact of sow heat stress (HS) on farrowing physiology and survival of the piglets. Pregnant primiparous sows (gilts) were allocated to either thermoneutral control (CON, n = 8; constant 20 °C) or cyclical HS conditions (n = 8; 0900 h to 1700 h, 30 °C; 1700 h to 0900 h, 28 °C) from d 110 of gestation until farrowing completion. Gilt respiration rate, skin temperature and rectal temperature were recorded daily, and farrowing duration was quantified by video analyses. Blood samples were collected from the piglet umbilical vein at birth. At 48 h of age, piglet growth was quantified by morphometric analyses. The thermal exposure model induced HS and respiratory alkalosis in the gilts, as indicated by increased respiration rate, rectal temperature, skin temperature (all P < 0.001), plasma cortisol (P = 0.01) and blood pH (P < 0.001). Heat-stressed gilts took longer to start expelling placentae (P = 0.003), although the active farrowing duration was not significantly different between treatments. Stillbirth rates were higher in the HS group (P < 0.001), with surviving piglets at birth having lower umbilical vein partial pressure of oxygen (P = 0.04), oxygen saturation rate (P = 0.03) and tending to have increased lactate concentrations (P = 0.07). At birth, piglet skin meconium staining scores were greater in the HS group (P = 0.022). At 48 h of age, piglets from the HS group had reduced small intestinal length (P = 0.02), reduced jejunal crypt depth (P = 0.02) and lighter absolute brain weight (P = 0.001). In contrast, piglet BW, growth rate, relative organ weight and small intestinal mucosal barrier function did not change between treatments. Collectively, these findings demonstrated gilt HS during late gestation caused farrowing complications and reduced the umbilical oxygen supply to the piglets at parturition, leading to increased risks of piglet stillbirth with implications on impaired neonatal survivability and development.

The first brain: Species comparisons and evolutionary implications for the enteric and central nervous systems.

BACKGROUND: The enteric nervous system (ENS) and the central nervous system (CNS) of mammals both contain integrative neural circuitry and similarities between them have led to the ENS being described as the brain in the gut. PURPOSE: To explore relationships between the ENS and CNS across the animal kingdom. We found that an ENS occurs in all animals investigated, including hydra, echinoderms and hemichordates that do not have a CNS. The general form of the ENS, which consists of plexuses of neurons intrinsic to the gut wall and an innervation that controls muscle movements, is similar in species as varied and as far apart as hydra, sea cucumbers, annelid worms, octopus and humans. Moreover, neurochemical similarities across phyla imply a common origin of the ENS. Investigation of extant species suggests that the ENS developed in animals that preceded the division that led to cnidaria (exemplified by hydra) and bilateria, which includes the vertebrates. The CNS is deduced to be a bilaterian development, later than the divergence from cnidaria. Consistent with the ENS having developed independent of the CNS, reciprocal connections between ENS and CNS occur in mammals, and separate neurons of ENS and CNS origin converge on visceral organs and prevertebral ganglia. We conclude that an ENS arose before and independently of the CNS. Thus the ENS can be regarded as the first brain.

Heterogeneity of enterochromaffin cells within the gastrointestinal tract.

Enterochromaffin cells were the first endocrine cells of the gastrointestinal tract to be chemically distinguished, almost 150 years ago. It is now known that the chromaffin reaction of these cells was due to their content of the reactive aromatic amine, 5-hydroxytryptamine (5-HT, also known as serotonin). They have commonly been thought to be a special class of gut endocrine cells (enteroendocrine cells) that are distinct from the enteroendocrine cells that contain peptide hormones. The study by Martin et al. in the current issue of this journal reveals that the patterns of expression of nutrient receptors and transporters differ considerably between chromaffin cells of the mouse duodenum and colon. However, even within regions, chromaffin cells differ; in the duodenum there are chromaffin cells that contain both secretin and 5-HT, cholecystokinin and 5-HT, and all three of secretin, cholecystokinin, and 5-HT. Moreover, the ratios of these different cell types differ substantially between species. And, in terms of function, 5-HT has many roles, including in appetite, motility, fluid secretion, release of digestive enzymes and bone metabolism. The paper thus emphasizes the need to define the many different classes of enterochromaffin cells and relate this to their roles.

Non-invasive respiratory support for infants with bronchiolitis: a national survey of practice.

BACKGROUND: Bronchiolitis is a common respiratory illness of early childhood. For most children it is a mild self-limiting disease but a small number of children develop respiratory failure. Nasal continuous positive airway pressure (nCPAP) has traditionally been used to provide non-invasive respiratory support in these children, but there is little clinical trial evidence to support its use. More recently, high-flow nasal cannula therapy (HFNC) has emerged as a novel respiratory support modality. Our study aims to describe current national practice and clinician preferences relating to use of non-invasive respiratory support (nCPAP and HFNC) in the management of infants (<12 months old) with acute bronchiolitis. METHODS: We performed a cross-sectional web-based survey of hospitals with inpatient paediatric facilities in England and Wales. Responses were elicited from one senior doctor and one senior nurse at each hospital. We analysed the proportion of hospitals using HFNC and nCPAP; clinical thresholds for their initiation; and clinician preferences regarding first-line support modality and future research. RESULTS: The survey was distributed to 117 of 171 eligible hospitals; 97 hospitals provided responses (response rate: 83%). The majority of hospitals were able to provide nCPAP (89/97, 91.7%) or HFNC (71/97, 73.2%); both were available at 65 hospitals (67%). nCPAP was more likely to be delivered in a ward setting in a general hospital, and in a high dependency setting in a tertiary centre. There were differences in the oxygenation and acidosis thresholds, and clinical triggers such as recurrent apnoeas or work of breathing that influenced clinical decisions, regarding when to start nCPAP or HFNC. More individual respondents with access to both modalities (74/106, 69.8%) would choose HFNC over nCPAP as their first-line treatment option in a deteriorating child with bronchiolitis. CONCLUSIONS: Despite lack of randomised trial evidence, nCPAP and HFNC are commonly used in British hospitals to support infants with acute bronchiolitis. HFNC appears to be currently the preferred first-line modality for non-invasive respiratory support due to perceived ease of use.

Restoration of intestinal function in an MPTP model of Parkinson's Disease.

Patients with Parkinson's disease often experience non-motor symptoms including constipation, which manifest prior to the onset of debilitating motor signs. Understanding the causes of these non-motor deficits and developing disease modifying therapeutic strategies has the potential to prevent disease progression. Specific neuronal subpopulations were reduced within the myenteric plexus of mice 21 days after intoxication by the intraperitoneal administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and was associated with a reduction in stool frequency, indicative of intestinal dysfunction. Oral administration of the divalent copper complex, Cu(II)(atsm), which has been shown to be neuroprotective and restore motor performance to MPTP lesioned mice, improved stool frequency and was correlated with restoration of neuronal subpopulations in the myenteric plexus of MPTP lesioned mice. Restoration of intestinal function was associated with reduced enteric glial cell reactivity and reduction of markers of inflammation. Therapeutics that have been shown to be neuroprotective in the central nervous system, such as Cu(II)(atsm), therefore also provide symptom relief and are disease modifying in the intestinal tract, suggesting that there is a common cause of Parkinson's disease pathogenesis in the enteric nervous system and central nervous system.

Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01.

BACKGROUND: It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. METHODS: Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. KEY RESULTS: HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. CONCLUSIONS & INFERENCES: HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists.

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes.

STUDY DESIGN: Focus Group. OBJECTIVES: To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand. SETTING: Australia. METHODS: A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion. RESULTS: A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities. CONCLUSION: This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of digestion.

The digestive systems of all species have been shaped by environmental pressures over long evolutionary time spans. Nevertheless, all digestive systems must achieve the same end points, the ingestion of biological material and its conversion to molecules that serve as energy substrates and structural components of tissues. A range of strategies to extract nutrients, including for animals reliant primarily on foregut fermentation, hindgut fermentation, and enzymatic degradation, have evolved. Moreover, animals have adapted to different foodstuffs as herbivores (including frugivores, folivores, granivores, etc.), carnivores, and omnivores. We present evidence that humans have diverged from other omnivores because of the long history of consumption of cooked or otherwise prepared food. We consider them to be cucinivores. We present examples to illustrate that the range of foodstuffs that can be efficiently assimilated by each group or species is limited and is different from that of other groups or species. Differences are reflected in alimentary tract morphology. The digestive systems of each group and of species within the groups are adaptable, with constraints determined by individual digestive physiology. Although overall digestive strategies and systems differ, the building blocks for digestion are remarkably similar. All vertebrates have muscular tubular tracts lined with a single layer of epithelial cells for most of the length, use closely related digestive enzymes and transporters, and control the digestive process through similar hormones and similarly organized nerve pathways. Extrapolations among species that are widely separated in their digestive physiologies are possible when the basis for extrapolation is carefully considered. Divergence is greatest at organ or organismal levels, and similarities are greatest at the cell and molecular level.

A ghrelin receptor agonist is an effective colokinetic in rats with diet-induced constipation.

BACKGROUND: Despite constipation being a common problem, the treatments that are available have side effects and are only partly effective. Recent studies show that centrally penetrant ghrelin receptor agonists cause defecation in humans and other species. Here, we describe some features of a rat model of low fiber-induced constipation, and investigate the effectiveness of the ghrelin agonist, capromorelin. METHODS: Rats were given low-fiber diets for 5 weeks. Their colorectal responsiveness to distension and to a behavioral test, water avoidance and colon histology were compared to those of rats on a standard diet. KEY RESULTS: After the low-fiber diet, distension of the colon produced fewer propulsive contractions, behaviorally induced defecation was reduced, and the lining of the colorectum was inflamed. However, capromorelin was similarly effective in causing defecation in constipated and non-constipated rats. CONCLUSIONS & INFERENCES: Low-fiber diet in rats produces a constipation phenotype, characterized by reduced responsiveness of the colorectum to distension and to a behavioral stimulus of defecation, water avoidance. The effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor stimulants may be effective in treating constipation.

Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers.

STUDY DESIGN: Single centre, single ascending dose study. OBJECTIVES: To compare the pharmacokinetics and assess the safety of capromorelin, a compound that has potential to treat constipation following spinal cord injury (SCI), in groups of able-bodied and SCI volunteers. SETTING: Local population from Victoria, Australia. METHODS: Following initial screening and baseline blood collections, participants received ascending oral doses (20, 50 and then 100 mg at least 1-week apart) of capromorelin after pre-dose blood collection, followed by blood collections over the following 12 h for pharmacokinetic analysis and 1-week and 4-week follow-up blood collections for safety evaluations. Blood pressure and heart rate were monitored. RESULTS: No serious adverse events were recorded following any dose in either the able-bodied group or the SCI group. There were no abnormal blood pressure or heart rate changes. Minor adverse events resolved quickly without the need for treatment. Pharmacokinetic behaviour was broadly similar between groups, with both exhibiting dose-dependent increases in Cmax and AUC0-∞. The SCI participants showed greater variance in pharmacokinetic parameters and had a slightly delayed Tmax and half-life. CONCLUSION: Capromorelin at the doses tested was safe and well tolerated in both SCI and able-bodied participants and also showed similar pharmacokinetics with dose-dependent increases in concentration and drug exposure.

Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet.

BACKGROUND: Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes. METHODS: Mice were fed a high-fat, high-cholesterol diet (21% fat, 2% cholesterol) or normal chow for 33 weeks. Liver injury was assessed by hematoxylin and eosin, picrosirius red staining, and measurement of plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different types of enteric neurons. KEY RESULTS: The mice developed steatosis, steatohepatitis, fibrosis, and a 10-fold increase in plasma ALT, indicative of liver disease. Oral glucose tolerance was unchanged. Loss and damage to enteric neurons occurred in the myenteric plexus of ileum, cecum, and colon. Total numbers of neurons were reduced by 15-30% and neurons expressing nitric oxide synthase were reduced by 20-40%. The RNA regulating protein, Hu, became more concentrated in the nuclei of enteric neurons after high-fat feeding, which is an indication of stress on the enteric nervous system. There was also disruption of the neuronal cytoskeletal protein, neurofilament medium. CONCLUSIONS & INFERENCES: Enteric neuron loss and damage occurs in animals with fatty liver disease in the absence of glucose intolerance. The enteric neuron damage may contribute to the gastrointestinal complications of fatty liver disease.

Non-perturbative calculation of molecular magnetic properties within current-density functional theory.

We present a novel implementation of Kohn-Sham density-functional theory utilizing London atomic orbitals as basis functions. External magnetic fields are treated non-perturbatively, which enable the study of both magnetic response properties and the effects of strong fields, using either standard density functionals or current-density functionals-the implementation is the first fully self-consistent implementation of the latter for molecules. Pilot applications are presented for the finite-field calculation of molecular magnetizabilities, hypermagnetizabilities, and nuclear magnetic resonance shielding constants, focusing on the impact of current-density functionals on the accuracy of the results. Existing current-density functionals based on the gauge-invariant vorticity are tested and found to be sensitive to numerical details of their implementation. Furthermore, when appropriately regularized, the resulting magnetic properties show no improvement over standard density-functional results. An advantage of the present implementation is the ability to apply density-functional theory to molecules in very strong magnetic fields, where the perturbative approach breaks down. Comparison with high accuracy full-configuration-interaction results show that the inadequacies of current-density approximations are exacerbated with increasing magnetic field strength. Standard density-functionals remain well behaved but fail to deliver high accuracy. The need for improved current-dependent density-functionals, and how they may be tested using the presented implementation, is discussed in light of our findings.

The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin.

BACKGROUND: Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action. METHODS: Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin. KEY RESULTS: Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 µg) to the lumbosacral spinal cord. CONCLUSIONS & INFERENCES: Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.

Gentamicin use in neonates: should we have a change of practice?

BACKGROUND: Gentamicin, one of the most commonly used antibiotics in neonates, has potential toxicity. This study was performed to determine the incidence of potential toxicity of gentamicin in term and preterm neonates. METHODS: A one-year retrospective study in neonates admitted to Special Baby Care Units at University Hospital of North Durham and Darlington Memorial Hospitals. We reviewed each admission and looked through the case notes in detail to document information about gentamicin administration, dosage and elevated gentamicin levels in the blood. Pre-third dose gentamicin levels >2 mg/L were classified as elevated. RESULTS: Overall, 192 babies (83 term and 109 preterm) had documented gentamicin levels. Of these, 43% (84/192) manifested elevated gentamicin levels. Of the babies with elevated gentamicin levels, 67% (56/84) weighed less than 2.5 kg. When a combination of gestation period and weight was considered, 61% (51/84) of preterm infants weighing <2.5 kg had elevated levels whereas only one term infant <2.5 kg exhibited elevated levels. CONCLUSION: Preterm neonates and specifically low birth weight neonates tolerate gentamicin poorly. Dosage and/or interval of administration of the medication may need modification in this group to minimise toxicity.

Nonruminant Nutrition Symposium: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract.

The functioning of the gastrointestinal tract is under the control of the most extensive system of peripheral neurons in the body, the enteric nervous system, and the largest endocrine system of the body, the GEP endocrine system. The enteric nervous system in large mammals contains 500 million neurons, and the GEP endocrine system produces more than 30 hormones. Numerous enteric neuropathies affecting both humans and animals have been described and digestive disorders affect commercially important species, such as horses and cattle. The most severe enteric neuropathies (e.g., lethal white syndrome in horses or Hirschsprung's disease in humans) can be fatal. Also, horses with ileus or other digestive disorders are commonly euthanized. In this review we discuss examples of enteric neuropathies that affect agricultural animals and humans: prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea. Enteric neurons and glia are a location of prion proteins and are involved in transmission of the infection from gut to brain and brain to gut. Postoperative ileus is a complex disorder involving the local inhibitory effects of sympathetic nervous system activation and the release of opioids, presumably from enteric neurons. Intestinal inflammation, especially of the external muscle that includes enteric ganglia, also occurs in ileus. Congenital distal bowel aganglionosis, responsible for lethal white syndrome in horses, Hirschsprung's disease in humans, and similar conditions in mice and rats, is a fatal condition if untreated. Mutations of the same genes can cause the condition in each of these species. The only effective current treatment is surgical removal of the aganglionic bowel. Infectious diarrheas involve activation of enteric secretomotor neurons by pathogens and the toxins they produce, which causes substantial fluid loss. Strategies to target enteric neurons in the treatment of secretory diarrheas have not been developed. Disorders of enteroendocrine cells, other than GEP endocrine tumors, are less well documented. However, evidence for the involvement of gut endocrine cells in a subset of patients with irritable bowel syndrome, and in the symptomology of celiac disease, has been demonstrated. Further investigation of the involvement of enteric neural and endocrine signaling systems in digestive disorders, especially in agricultural and companion animals, may lead to diagnostic and therapeutic advances.

The involvement of nitric oxide synthase neurons in enteric neuropathies.

Nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS) is a transmitter of inhibitory neurons supplying the muscle of the gastrointestinal tract. Transmission from these neurons is necessary for sphincter relaxation that allows the passage of gut contents, and also for relaxation of muscle during propulsive activity in the colon. There are deficiencies of transmission from NOS neurons to the lower esophageal sphincter in esophageal achalasia, to the pyloric sphincter in hypertrophic pyloric stenosis and to the internal anal sphincter in colonic achalasia. Deficits in NOS neurons are observed in two disorders in which colonic propulsion fails, Hirschsprung's disease and Chagas' disease. In addition, damage to NOS neurons occurs when there is stress to cells, in diabetes, resulting in gastroparesis, and following ischemia and reperfusion. A number of factors may contribute to the propensity of NOS neurons to be involved in enteric neuropathies. One of these is the failure of the neurons to maintain Ca(2+) homeostasis. In neurons in general, stress can increase cytoplasmic Ca(2+), causing a Ca(2+) toxicity. NOS neurons face the additional problem that NOS is activated by Ca(2+). This is hypothesized to produce an excess of NO, whose free radical properties can cause cell damage, which is exacerbated by peroxynitrite formed when NO reacts with oxygen free radicals.

Investigation of the presence of ghrelin in the central nervous system of the rat and mouse.

Ghrelin and ghrelin receptor agonist have effects on central neurons in many locations, including the hypothalamus, caudal brain stem, and spinal cord. However, descriptions of the distributions of ghrelin-like immunoreactivity in the CNS in published work are inconsistent. We have used three well-characterized anti-ghrelin antibodies, an antibody to the unacylated form of ghrelin, and a ghrelin peptide assay in rats, mice, ghrelin knockout mice, and ghrelin receptor reporter mice to re-evaluate ghrelin presence in the rodent CNS. The stomach served as a positive control. All antibodies were effective in revealing gastric endocrine cells. However, no specific staining could be found in the brain or spinal cord. Concentrations of antibody 10 to 30 times those effective in the stomach bound to nerve cells in rat and mouse brain, but this binding was not reduced by absorbing concentrations of ghrelin peptide, or by use of ghrelin gene knockout mice. Concentrations of ghrelin-like peptide, detected by enzyme-linked immunosorbent assay in extracts of hypothalamus, were 1% of gastric concentrations. Ghrelin receptor-expressing neurons had no adjacent ghrelin immunoreactive terminals. It is concluded that there are insignificant amounts of authentic ghrelin in neurons in the mouse or rat CNS and that ghrelin receptor-expressing neurons do not receive synaptic inputs from ghrelin-immunoreactive nerve terminals in these species.