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Canna~Fangled Abstracts

Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids.

By April 17, 2013No Comments

Pub Med

Nat Neurosci. 2013 Jan 27. doi: 10.1038/nn.3321. [Epub ahead of print]

Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids.


1] Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada. [2] Department of Psychiatry, Center for Psychiatric Neuroscience, Site de Cery, Lausanne University Hospital, Lausanne, Switzerland. [3].


The prevalence of obesity has markedly increased over the past few decades. Exploration of how hunger and satiety signals influence the reward system can help us understand non-homeostatic feeding. 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 long-term depression (LTD) of mouse 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, insulin-induced LTD is occluded. Finally, insulin in the VTA reduces food anticipatory behavior in mice and conditioned place preference for food in rats. Taken together, these results suggest that insulin in the VTA suppresses excitatory synaptic transmission and reduces anticipatory activity and preference for food-related cues.