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Updated: May 18, 2026

Simultaneous Detection of c-Fos Activation from Mesolimbic and Mesocortical Dopamine Reward Sites Following Naive Sugar and Fat Ingestion in Rats
Published on: August 24, 2016
A food-associated CS activates c-Fos in VTA DA neurons and elicits conditioned approach
Karen Kest1, Ivonne Cruz, Dan Hong Chen
1Graduate Center, City University of New York, United States.
Abstract:
Neutral stimuli associated with unconditioned stimuli (USs) acquire the ability to act as conditioned stimuli (CSs), which can elicit behaviors similar to the US with which they are associated. The neural mechanisms by which this occurs are not fully known. We have previously proposed a model stipulating CSs function as such because they acquire the capacity to activate dopamine (DA) neurons at the level of the ventral tegmental area (VTA). In the present experiments we hypothesized that a food-associated CS (light), which demonstrably functions as such by eliciting conditioned responses (CRs), comes to acquire the capacity to activate VTA DA neurons. In Experiment 1, rats were allowed to eat or not eat food (food being the US). In Experiment 2, rats were trained to retrieve food pellets after light presentations (the CS) and then tested for the expression of the food checking response (the CR) with only CS presentations. In Experiment 1, eating food (exposure to the US) caused a significantly greater number of VTA DA (TH-labeled) cells to express c-Fos than not eating. In Experiment 2, CS (light) presentations caused a significant amount of conditioned approach and a significantly greater number of VTA TH-labeled (DA) cells to express c-Fos. These findings support our model stipulating that conditioned approach learning occurs when CSs acquire the capacity to cause conditioned activation of VTA DA neurons.
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