Posted by Phillipa on July 13, 2012, at 20:50:40
Big topic here ahedonia. New research. Phillipa
From Medscape Medical News > PsychiatryHormone a New Treatment Target for Depression, Schizophrenia?
Megan Brooks
Authors and Disclosures
July 11, 2012 The naturally occurring hormone melanocortin may provide a novel target for treating anhedonia, a common symptom of major depression as well as other neuropsychiatric disorders, including schizophrenia, a new animal study suggests.
Investigators at Stanford University School of Medicine in California led by Robert Malenka, MD, PhD, observed that melanocortin, which is known to affect appetite, turns off the brain's ability to experience pleasure in the presence of stress.
"This is the first study to suggest that we should look at the role of melanocortin in depression-related syndromes," Eric Nestler, MD, PhD, of the Friedman Brain Institute at Mount Sinai School of Medicine in New York City, who was not involved in the study, commented in a statement from Stanford University.
Their research was published online July 11 in Nature.
Critical Synaptic Changes
Chronic stress is a strong contributor to depression, and depression often leads to a variety of symptoms, including anhedonia.
"Although hypotheses defining the neural pathophysiology of depression have been proposed, the critical synaptic adaptations in key brain circuits that mediate stress-induced depressive symptoms remain poorly understood," the investigators write.
"A few scattered studies had suggested that chronic stress increased melanocortin levels in the brain," Dr. Malenka added in a statement. "And it was known that stressed animals have heightened numbers of receptors for melanocortin in the nucleus accumbens."
But it was not known whether melanocortin actually affected the nucleus accumbens, or how. "We wanted to find out, because we were wondering if by modulating melanocortin's activity with a drug we could relieve or prevent a major symptom of depression," said Dr. Malenka.
The researchers report that chronic stress in mice leads to activation of the melanocortin 4 receptor, which decreases the strength of excitatory synapses on neurons expressing D1 dopamine receptor in the nucleus accumbens, the brain's pleasure center.
The research also shows that stress-elicited increases in behavioral measurements of anhedonia in the mice can be prevented by blocking melanocortin 4 receptormediated synaptic changes in the animals.
"By delineating the molecular mechanisms underlying the circuit modifications that mediate specific behavioural manifestations of psychiatric symptoms such as anhedonia, it should be possible to accelerate the development of efficacious therapies with new mechanisms of action," the investigators write.
Beyond DepressionDr. Malenka points out that the melanocortin pathway is already on drug companies' radar screens, because it appears to be involved in appetite disorders. Melanocortin mimics and inhibitors have been developed that could be used in clinical tests to determine whether managing patients' melanocortin signaling relieves anhedonia.
The implications may go beyond treatments for depression because anhedonia manifests in other neuropsychiatric syndromes, such as schizophrenia, as well as in terminally ill people who have given up hope, the researchers note.
The study was funded by the National Institutes of Health and the Davis Foundation Program in Eating Disorders Research. The authors have disclosed no relevant financial relationships
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