The μ-opioid receptor agonist DAMGO presynaptically suppresses solitary tract-evoked input to neurons in the rostral solitary nucleus

• Published in: Journal of neurophysiology Vol. 109; no. 11; pp. 2815 - 2826
• Main Authors: Boxwell, Alison J., Yanagawa, Yuchio, Travers, Susan P., Travers, Joseph B.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2013
• Subjects: Animals; Enkephalin, Ala-MePhe-Gly- - pharmacology; Evoked Potentials; GABAergic Neurons - drug effects; GABAergic Neurons - physiology; Mice; Miniature Postsynaptic Potentials; Neural Inhibition; Neurotransmitter Agents - pharmacology; Receptors, Opioid, mu - agonists; Solitary Nucleus - cytology; Solitary Nucleus - drug effects; Solitary Nucleus - physiology; Synapses - drug effects; Synapses - physiology; GABA; GAD67-GFP knockin mouse; taste; disinhibition
• ISSN: 0022-3077; 1522-1598; 1522-1598
• DOI: 10.1152/jn.00711.2012

Taste processing in the rostral nucleus of the solitary tract (rNST) is subject to modulatory influences including opioid peptides. Behavioral pharmacological studies suggest an influence of μ-opioid receptors in rNST, but the underlying mechanism is unknown. To determine the cellular site of action, we tested the effects of the μ-opioid receptor agonist DAMGO in vitro. Whole cell patch-clamp recordings were made in brain stem slices from GAD67-GFP knockin mice expressing enhanced green fluorescent protein (EGFP) under the control of the endogenous promoter for GAD67, a synthetic enzyme for GABA. Neuron counts showed that ∼36% of rNST neurons express GABA. We recorded monosynaptic solitary tract (ST)-evoked currents (jitter ≤ 300 μs) in both GAD67-EGFP-positive (GAD67+) and GAD67-EGFP-negative (GAD67−) neurons with equal frequency (25/31; 22/28), but the inputs to the GAD67+ neurons had significantly smaller paired-pulse ratios compared with GAD67− neurons. DAMGO (0.3 μM) significantly suppressed ST-evoked currents in both cell types (mean suppression = 46 ± 3.3% SE), significantly increased the paired-pulse ratio of these currents, and reduced the frequency of spontaneous miniature excitatory postsynaptic currents but did not diminish their amplitude, indicating a presynaptic site of action. Under inhibitory amino acid receptor blockade, DAMGO was significantly more suppressive in GAD67+ neurons (59% reduction) compared with GAD67− neurons (35% reduction), while the reverse was true in normal artificial cerebrospinal fluid (GAD67+: 35% reduction; GAD67−: 57% reduction). These findings suggest that DAMGO suppresses activity in rNST neurons predominantly via a presynaptic mechanism, and that this effect may interact significantly with tonic or evoked inhibitory activity.