Dopamine responsiveness in Nucleus Accumbens Shell and Core and Prefrontal Cortex during operant behavior for sucrose

Dopamine is implicated in the responsiveness to rewarding properties of natural and pharmacological stimuli. Conditioned stimuli (CS), linked to rewards such as food or drugs of abuse (uncontidioned stimuli, US), are essential to support the motivated behaviour. The role of mesocortical and mesolimbic DA in response to food CS after instrumental paradigm still remains unclear. The aim of our study was to investigate by microdialysis the impact of instrumental food CSs and US on behaviour and on basal DA in three terminal DA areas: shell and core of nucleus accumbens (NAc) and medial prefrontal cortex (mPFCX), using a food self-administration paradigm. Rats were trained to acquire sucrose self-administration under a Fixed Ratio 1 (FR 1) or FR5 variable time out schedule of responding. After training, animals were able to self-administer sucrose pellets and microdialysis coupled with self-administration experiments were performed.. The main finding of our study was that NAc shell DA has been activated not only by the conditioned cues but also by food after the instrumental conditioning. When both stimuli are presented in the same moment the increase of DA is strengthened and prolonged. DA response was obtained in NAc core only during US presentation. mPFCX has been activated by each component of motivated behaviour, except for the response to CS using a FR5 schedule. We can conclude that DA in the NAc shell plays an important role on the acquisition and expression of motivated behaviour in food consumption, whereas NAc core and PFCX are less implicated. This study provides a robust and reproducible model for a parametric study of the relationship between behaviour and DA transmission in the NAc shell and core and in the mPFCX .