Boxwell AJ, Yanagawa Y, Travers SP, Travers JB. The -opioid receptor agonist DAMGO presynaptically suppresses solitary tract-evoked input to neurons in the rostral solitary nucleus. J Neurophysiol 109: 2815-2826, 2013. First published March 13, 2013 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 -opioid receptors in rNST, but the underlying mechanism is unknown. To determine the cellular site of action, we tested the effects of the -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 ϳ36% of rNST neurons express GABA. We recorded monosynaptic solitary tract (ST)-evoked currents (jitter Յ 300 s) in both GAD67-EGFP-positive (GAD67ϩ) and GAD67-EGFP-negative (GAD67Ϫ) neurons with equal frequency (25/31; 22/28), but the inputs to the GAD67ϩ neurons had significantly smaller paired-pulse ratios compared with GAD67Ϫ neurons. DAMGO (0.3 M) significantly suppressed ST-evoked currents in both cell types (mean suppression ϭ 46 Ϯ 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 GAD67ϩ neurons (59% reduction) compared with GAD67Ϫ neurons (35% reduction), while the reverse was true in normal artificial cerebrospinal fluid (GAD67ϩ: 35% reduction; GAD67Ϫ: 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.