Insulin induces long-term depression of VTA dopamine neurons via an endocannabinoid-mediated mechanism
| Autor: | Subashini Karunakaran, Haiyan Zou, Shuai Liu, Anthony G. Phillips, Stephanie L. Borgland, Benjamin Boutrel, Carine Dias, Jovi C Y Wong, Gwenaël Labouèbe, Susanne M. Clee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
obesity CB1 receptor medicine.medical_treatment Dopamine Synaptic Transmission Rats Sprague-Dawley Mice 0302 clinical medicine Insulin Long-term depression AMPA receptors incentive salience 0303 health sciences Behavior Animal TOR Serine-Threonine Kinases General Neuroscience Glutamate receptor Endocannabinoid system conditioned place preference Ventral tegmental area medicine.anatomical_structure Excitatory postsynaptic potential LTD psychological phenomena and processes Signal Transduction medicine.drug Glutamic Acid Biology Article 03 medical and health sciences medicine Animals 030304 developmental biology Dopaminergic Neurons Long-Term Synaptic Depression Ventral Tegmental Area Association Learning Feeding Behavior endocannabinoid Dietary Fats Conditioned place preference Rats Mice Inbred C57BL nervous system Synapses Proto-Oncogene Proteins c-akt Neuroscience 030217 neurology & neurosurgery Endocannabinoids |
| Zdroj: | Nature neuroscience Nature Neuroscience, vol. 16, no. 3, pp. 300-308 |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | The prevalence of obesity has drastically increased over the last few decades. Exploration into how hunger and satiety signals influence the reward system can help us to understand non-homeostatic mechanisms of feeding. Evidence suggests that insulin may act in the ventral tegmental area (VTA), a critical site for reward-seeking behavior, to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA remain unknown. We demonstrate that insulin, a circulating catabolic peptide that inhibits feeding, can induce a long-term depression (LTD) of excitatory synapses onto VTA dopamine neurons. This effect requires endocannabinoid-mediated presynaptic inhibition of glutamate release. Furthermore, after a sweetened high fat meal, which elevates endogenous insulin levels, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior and conditioned place preference for food. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces salience of food-related cues. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|