Dopamine receptor signaling in the medial orbital frontal cortex and the acquisition and expression of fructose-conditioned flavor preferences in rats

•Fructose conditioned flavor preferences (FCFP).•Medial orbitofrontal cortex (MOFC) dopamine D2 antagonism reduced FCFP expression.•Dorsolateral prefrontal D2 antagonism failed to affect FCFP expression.•MOFC dopamine D1 antagonism failed to affect FCFP expression.•FCFP acquisition was unaffected by MOFC D1 and D2 antagonists.

Systemic dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC) antagonists blocked fructose-conditioned flavor preference (CFP) acquisition and expression. Fructose-CFP acquisition was eliminated by medial prefrontal cortex (mPFC) SCH and mPFC or amygdala (AMY) RAC. Fructose-CFP expression was reduced following SCH or RAC in AMY or nucleus accumbens (NAc). The present study examined fructose-CFP acquisition and expression following SCH and RAC in the medial orbital frontal cortex (MOFC), another ventral tegmental area DA target. For fructose-CFP acquisition, five groups of rats received vehicle, SCH (24 or 48 nmol) or RAC (24 or 48 nmol) in the MOFC 0.5 h prior to 8 training sessions with one flavor (CS+/Fs) mixed in 8% fructose and 0.2% saccharin, and another flavor (CS−/s) mixed in 0.2% saccharin. In six 2-bottle choice tests in 0.2% saccharin, similar fructose-CFP preferences occurred in groups trained with vehicle (76–77%), SCH24 (69–78%), SCH48 (70–74%) and RAC48 (85–92%). RAC24-trained rats displayed significant CS+ preferences during the first (79%) and third (71%), but not second (58%) test pair. For fructose-CFP expression, rats similarly trained with CS+/Fs and CS− solutions received 2-bottle choice tests following MOFC injections of SCH or RAC (12–48 nmol). CS+ preference expression was significantly reduced by RAC (48 nmol: 58%), but not SCH relative to vehicle (78%). A control group receiving RAC in the dorsolateral prefrontal cortex displayed fructose-CFP expression similar to vehicle. These data demonstrate differential frontal cortical DA mediation of fructose-CFP with mPFC D1 and D2 signaling exclusively mediating acquisition, and MOFC D2 signaling primarily mediating expression.