Regulation of feeding by lateral hypothalamic gabaergic neurons during acute morphine administration in mice

Authors

• A Garcia
• P Miranda
• H Kim
• S Sarsfield
• Y Aponte

Abstract

The prevalence of obesity has grown rapidly over the past several decades along with an increase in the incidence of chronic pain and prescription opioid use. In preclinical studies, opioids have been associated with a preference for sugary and fatty food consumption. It has been well established that activation of lateral hypothalamic GABAergic neurons, which express the vesicular GABA transporter (LH VGAT), induces voracious feeding of palatable and non-palatable foods. However, LH VGAT regulation of feeding behaviors and body weight during opioid dependence remains unknown. Our preliminary data show a decrease in LH VGAT neuronal excitability after applying morphine (10 µM) in brain slices. Subsequently, we examinedwhether simultaneous activation of LH VGAT neurons during acute morphine administration had an effect on food intake and body weight. Both chemogenetic and optogenetic activation of LHVGAT neurons reduced the anorexigenic effect induced by acute morphine administration and increased exploration in the food zone. Additionally, hyperlocomotion caused by morphine was occluded by the activation of these neurons. In future experiments, we aim to determine whether activation of LH VGAT neurons during morphine dependence has an effect in feeding. In addition, we will examine whether LH VGAT neuronal activity is affected after morphine administration in mice kept on a regular or high-fat diet.

Scientific Focus Area: Neuroscience

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