Activation of µ-opioid receptors in the rostral ventrolateral medulla blocks the sympathetic counter-regulatory response to glucoprivation.

Activation of neurons in the rostral ventrolateral medulla (RVLM) following glucoprivation initiates sympathoadrenal activation, adrenaline release, and increased glucose production. Here, we aimed to determine the role of RVLM µ-opioid receptors in the counter-regulatory response to systemic glucoprivation. Experiments were performed in sodium pentobarbital anaesthetised male Sprague-Dawley rats (n=30). Bilateral activation of RVLM µ-opioid receptors with DAMGO (8mM, 50nl) depressed adrenal sympathetic nerve activity (ASNA), for ~60 minutes (n=6; Δ 49.9±5.8%, P<0.05). The counter-regulatory response to glucoprivation (measured by adrenal sympathetic efferent nerve activity) induced by 2-deoxyglucose (2-DG) (n=6; Δ63.6±16.5%, P<0.05) was completely blocked 60 minutes after DAMGO microinjections (n=6; Δ-10.2±3.5%, P<0.05). Furthermore, DAMGO pre-treatment attenuated the increase in blood glucose levels following 2-DG infusion (n=6; 6.1±0.7mmol/L vs baseline 5.2±0.3mmol/L, P>0.05) compared to 2-DG alone (n=6; 7.6±0.4mmol/L vs baseline 6.0±0.4mmol/L, P<0.05). Thus, activation of RVLM µ-opioid receptors attenuated the neural efferent response to glucoprivation, and reduced glucose production.