Neuroendocrine Pharmacology
Obesity
Obesity is an increasing problem in our community and leads to increased risk of diabetes and high blood pressure. The brain regulates appetite through the action of chemicals that either increase or decrease feeding. Neuropeptide Y (NPY) is present in the brains of mammals and causes increased food intake. Alterations in brain NPY have been described in animal models of obesity.
Our laboratory uses animal models of obesity to explore the brain mechanisms involved in appetite, and the changes that occur in these systems during the development of obesity. Animals, like humans, develop obesity if they overeat highly palatable food. Approaches used in our laboratory include measurement of food intake in response to administration of different agents alone or in combination to rats, determining the effect of these agents on brain chemistry, and examining whether the feeding responses is altered in obese animals. Our work has shown that obese animals do respond differently to control animals. Information like this will provide new insight into potential treatments for obesity and other feeding disorders. The regulation of feeding is a critical process, with many overlapping systems protecting this vital function. Our work aims to improve our understanding of how these systems interact to regulate feeding.
Diabetes
The ability to accurately sense changes in glucose is critical to the survival of children with Type 1 diabetes. Glucose and insulin regulate the hypothalamic release of neuropeptides and noradrenaline. Our laboratory is investigating whether lowered glucose affects neurotransmitter release in the brain, as this may contribute to the problem of hypoglycemia unawareness, a life threatening complication of diabetes. We are currently investigating the involvement of novel brain transmitters in glucose sensing and the role of alternative fuels such as lactate in the response to hypoglycemia. Improving our understanding of glucose sensing will eventually aid in averting this life threatening complication.
Epilepsy
Work carried out in collaboration with Associate Professor Terry O’Brien, Royal Melbourne Hospital, is examining the involvement of NPY in a genetic model of absence–type epilepsy. NPY is known to regulate neuronal excitability, and animals that lack NPY are prone to seizures. Our preliminary data in epileptic animals suggest NPY is altered in critical brain regions important in generating seizure-like activity. Current work is extending this finding. If confirmed, these experiments have the potential to identify novel targets for future anti-epileptic drugs.
Researchers
Dr Jillian Pavia
Ms Elena Velkoska
Ms Larissa Prior
Dr. Hui Chen
Mr. Edwin Kiat
Selected Publications
Chaffer C and
Morris MJ. The feeding response to melanin concentrating hormone is attenuated by Y1 receptor blockade.
Endocrinology 2002;143:191-197.
Chen H, Vlahos R, Bozinovski S, Jones J, Anderson GP,
Morris MJ. Effect of short-term cigarette smoke exposure on body weight, appetite and brain neuropeptide Y in mice.
Neuropsychopharmacology. 2005 Apr; 30(4):713-9.
Gozali M, Pavia JM and
Morris MJ. Involvement of neuropeptide Y in glucose sensing in the dorsal hypothalamus of streptozotocin diabetic rats- in vitro and in vivo studies of transmitter release
Diabetologia 2002;45:1332-1339.
Hansen MJ, Jovanovska V and
Morris MJ. Adaptive responses in hypothalamic neuropeptide Y in the face of prolonged high fat feeding in the rat. J
Neurochemistry 2004;88:909-916.
Hansen MJ and
Morris MJ. Evidence for an interaction between neuropeptide Y and the melanocortin-4 receptor on feeding in the rat.
Neuropharmacology 2002;42:792-797.
Hansen MJ, Schioth HB,
Morris MJ. Feeding responses to a melanocortin agonist and antagonist in obesity induced by a palatable high-fat diet.
Brain Research. 2005; 1039(1-2):137-45.
Morris MJ Cardiovascular effects of neuropeptide Y In
Handbook Exp Pharmacology Vol 160 2004 ED M Michel (Springer)
Morris MJ and Pavia JM. Increased endogenous noradrenaline and neuropeptide Y release from the hypothalamus of streptozotocin diabetic rats.
Brain Research 2004;1006:100-6.
Taher TR, Salzberg M,
Morris MJ, Rees S, O'Brien TJ. Chronic low-dose corticosterone supplementation enhances acquired epileptogenesis in the rat amygdala kindling model of TLE.
Neuropsychopharmacology. 2005 30:1610-6.
Morris MJ, Velkoska E, Cole TJ. Central and peripheral contributions to obesity associated hypertension: impact of early overnourishment.
Exp. Physiol 2005;90(5):697-702.
Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y axis to promote weight Loss.
American Journal of Respiratory and Critical Care Medicine. 2006; published ahead of print on March 10, 2006 as doi:10.1164/rccm.200506-977OC