Evaluation of saccharin intake and expression of fructose-conditioned flavor preferences following opioid receptor antagonism in the medial prefrontal cortex, amygdala or lateral hypothalamus in rats.

In prior studies, systemic opioid receptor antagonism with naltrexone (NTX) failed to block flavor preference conditioning by the sweet taste or post-oral actions of sugar despite reducing overall flavored saccharin intake. Further, NTX microinjections into the nucleus accumbens (NAc) shell or core failed to alter the expression of preferences conditioned by the sweet taste or post-oral actions of sugars. In contrast, fructose-conditioned flavor preferences (CFP) were reduced or eliminated by systemic or intracerebral administration of dopamine (DA) D1 or D2 antagonists in the NAc, medial prefrontal cortex (mPFC), amygdala (AMY) or lateral hypothalamus (LH). The present study examined whether NTX microinjections into the mPFC, AMY or LH would alter expression of fructose-CFP and total flavored saccharin intake. Food-restricted rats with bilateral cannulae aimed at the mPFC, AMY or LH were trained to drink a fructose (8%)+saccharin (0.2%) solution mixed with one flavor (CS+, e.g., cherry) and a 0.2% saccharin solution mixed with another flavor (CS-, e.g., grape) during 10 one-bottle sessions. Two-bottle tests with the cherry and grape flavors in 0.2% saccharin solutions occurred 10min following total bilateral NTX doses of 0, 1, 25 and 50µg administered into the mPFC, AMY or LH. Rats preferred the CS+ over CS- flavor following vehicle and all NTX doses administered into either the mPFC or LH. CS+ intake was significantly greater than CS- intake following vehicle and the low NTX dose in the AMY; however, at the 25 and 50µg AMY NTX doses, CS+ intakes did not significantly exceed CS- intakes. Total flavored saccharin intake was significantly reduced by all three LH NTX doses (20-35%), by the 25 (14%) and 50 (22%)µg AMY NTX doses, but not by mPFC NTX. Thus, opioid antagonism in the AMY, but not the mPFC or LH attenuated, but did not block the expression of fructose-CFP, and LH and AMY, but not mPFC, NTX significantly reduced total saccharin intake. Therefore, whereas opioid antagonism in the LH and AMY reduces sweet intake, they appear less effective in altering fructose-CFP.

Dopamine signaling in the medial prefrontal cortex and amygdala is required for the acquisition of fructose-conditioned flavor preferences in rats.

Systemic administration of dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC) antagonists blocked both acquisition and expression of fructose-conditioned flavor preferences (CFP). It is unclear what brain circuits are involved in mediating these effects. The present study investigated DA signaling within the nucleus accumbens shell (NAcS), amygdala (AMY) and medial prefrontal cortex (mPFC) in the acquisition and expression of fructose-CFP. In Experiment 1, separate groups of rats were injected daily in the NAcS or AMY with saline, SCH (24 nmol) or RAC (24 nmol) prior to training sessions with a flavor (CS+) mixed with 8% fructose and 0.2% saccharin (CS+/F) and a different flavor (CS-) mixed with only 0.2% saccharin. In the two-bottle choice tests with 0.2% saccharin, only rats injected with RAC in the AMY failed to acquire a CS+ preference (45-54%). In Experiment 2, new rats were identically trained, but saline, SCH and RAC were injected in the mPFC. In subsequent two-bottle choice tests, SCH- and RAC-treated rats failed to exhibit a CS+ preference (50-56%). In Experiment 3, new rats were trained with CS+/F and CS- without injections. Subsequent two-bottle choice tests were then conducted following bilateral injections of SCH or RAC in the mPFC at total doses of 0, 12, 24 and 48 nmol. Expression of the CS+ preference failed to be affected by either antagonist, indicating that the mPFC is not involved in the maintenance of this preference. These data indicate that the acquisition of fructose-CFP is dependent on DA signaling in the mPFC and AMY.