Lateral septum mu opioid receptors in stimulation of feeding

Stimulation of mu opioid receptors using drugs like morphine can increase eating when injected into multiple brain regions including the lateral septum (LS). The LS has been classically associated with reward, anxiety and fearful behaviors but more recently has also received attention with regard to control of feeding. To investigate the role of LS opioid receptors in feeding, we injected mu, delta, and kappa opioid receptor agonists and a mu specific receptor antagonist directly into the LS of rats. We expected that if feeding is mu receptor specific then only mu receptor agonists would increase feeding. We also hypothesized that mu receptor antagonists would suppress the feeding elicited by mu receptor agonists like morphine. Further, because the LS is densely populated with GABA receptors, we used the GABA_A receptor agonist muscimol to assess the effect of inhibition of LS neurons on feeding. Our results show that the mu receptor agonist morphine and the specific mu agonist DAMGO reliably and significantly increase feeding behavior across doses tested, while delta and kappa agonists were ineffective. CTAP, a specific mu receptor antagonist, at low doses unexpectedly increased morphine-elicited feeding but at high doses decreased morphine's effect, consistent with mediation by mu receptors. Finally, muscimol rapidly elicited feeding, suggesting a role for LS GABA_A receptors in feeding stimulation. These findings suggest that mu opioid receptors in the LS play complex roles in feeding and that neural inhibition may be a mechanism by which they elicit feeding.