Hypothalamic ghrelin signaling in cannabis induced feeding
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Cannabis is the most widely used illicit drug worldwide. In this context, vaporization is the most common route of cannabis administration. Data from our lab indicates that vapor cannabis exposure increases meal frequency while decreasing meal size. Increasing appetite can help patients with cancer or AIDS who often suffer from anorexia. In addition to meal size, data indicates an increase in plasma levels of the appetite-stimulating hormone, ghrelin, following cannabis exposure. Once ghrelin is released from the gastrointestinal (GI) tract, it acts on the ghrelin-1a receptors (GHSR-1a) in the CNS to stimulate appetite. Preliminary experiments from our lab indicate that blockade of ghrelin secretion, or blockade of GHSR-1a activity reduces cannabis induced feeding. Importantly ghrelin targets agouti related peptide (AgRP) neurons in the hypothalamus to stimulate appetite. The goal of this project is to determine if ghrelin signaling in AgRP neurons regulates cannabis induced feeding. To do this, we will utilize genetic loss of function (LOF) mice that lack GHSR-1a exclusively on AgRP neurons (AgRP-GHSR fxl/fxl). We will expose AgRP-GHSR fxl/fxl and wild type (WT) mice to vapor cannabis, and subsequently measure food intake.