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 counterregulatory response to systemic glucoprivation. Experiments were performed in pentobarbital sodium anesthetized male Sprague-Dawley rats ( n = 30). Bilateral activation of RVLM µ-opioid receptors with [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) (8 mM, 50 nl) depressed adrenal sympathetic nerve activity for ~60 min ( n = 6; Δ49.9 ± 5.8%, P < 0.05). The counterregulatory 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 min after DAMGO microinjections ( n = 6; Δ10.2 ± 3.5%, P < 0.05). Furthermore, DAMGO pretreatment attenuated the increase in blood glucose levels after 2-DG infusion ( n = 6; 6.1 ± 0.7mmol/l vs. baseline 5.2 ± 0.3mmol/l, P > 0.05) compared with 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.
Keywords: DAMGO; RVLM; adrenal nerve; glucose; sympathetic.