Opioids, palatable feeding and exercise

In the thesis, we studied the functional cross-talk between mu and delta opioid receptors in rewarding conditions elicited by natural stimuli such as palatable food and/or exercise or by drugs of abuse such as morphine. Using mu-mCherry/delta-eGFP double knock-in mice, we showed that mu-delta heteromerization alters mu opioid receptor signaling and trafficking in response to the endogenous opioid peptide met-enkephalin, but not β-endorphin, in primary hippocampal cultures and in vivo. We also showed that chronic morphine administration extended mu-delta neuronal co-expression throughout the brain which persisted after 4 weeks abstinence, pointing to morphine-induced long- lasting changes. In the second part of the thesis, neuroanatomical connections of the subfornical area of the lateral hypothalamus (LHsf) were mapped in mice and examined the activation of mu and delta receptors in this region following fasting and refeeding in HF diet and chow diet. Within the LHsf, which was reciprocally connected to many hypothalamic and reward related brain areas, fasting internalized delta receptors irrespective to the diet regimen whereas refeeding differentially activated mu and receptors in chow-fed and HFD-fed animals. Finally, opioid system related gene expression was measured in the long-term fc-HFHS fed and voluntary wheel running rats, which only revealed an interaction effect for delta opioid receptor expression in the LH.