Long-acting ghrelin mimetics (MK-677) negatively affect fear processing. (MK-677!)

Study:
[A ghrelin–growth hormone axis drives stress-induced vulnerability to enhanced fear, RM Meyer, Molecular Psychiatry \(2014\), 1284 – 1294](
http://www.nature.com/mp/journal/v19/n12/full/mp2013135a.html)

Here we demonstrate changes in endogenous ghrelin following stress and also use a low-dose, long-acting agonist to replicate the naturally occurring ghrelin state. We also provide clear evidence that acute and chronic ghrelin receptor manipulations have profoundly different effects. It is important to note that the changes in fear reported here occurred following small, but persistent, changes in ghrelin signaling, and all were in the absence of any locomotor effects.

We suggest that the utility of ghrelin in the stress response may be similar to glucocorticoids: under ‘normal’ conditions, there is an optimal level of the hormone, and too little, or too much hormonal signaling can lead to dysfunction in neuronal circuits. Repeated activation of ghrelin and glucocorticoid pathways together contributes to stress-induced ‘load’ on the body. In this regard, heightened ghrelin signaling may have both advantageous and undesirable consequences, but these must be ca…