Activation of nucleus accumbens mu-opioid receptors enhances the response to a glycaemic challenge

Opioids are known to affect blood glucose levels but their exact role in the physiological control of glucose metabolism remains unclear. Although there are numerous studies investigating the peripheral effects of opioid stimulation, little is known about how central opioids control blood glucose and which brain areas are involved. One brain area possibly involved is the nucleus accumbens because, as well as being a key site for opioid effects on food intake, it has also been implicated in the control of blood glucose levels. Within the nucleus accumbens, mu-opioid receptors are most abundantly expressed. Therefore, in the present study, we investigated the role of mu-opioid receptors in the nucleus accumbens in the control of glucose metabolism. We show that infusion of the mu-opioid receptor agonist [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin (DAMGO) in the nucleus accumbens by itself does not affect blood glucose levels, but it enhances the glycaemic response after both an insulin tolerance test, as well as a glucose tolerance test. These findings indicate that the nucleus accumbens plays a role in the central effects of opioids on glucose metabolism, and highlight the possibility of nucleus accumbens mu-opioid receptors as a therapeutic target for enhancing the counter-regulatory response.