title: The μ-opioid receptor agonist DAMGO presynaptically suppresses solitary tract-evoked input to neurons in the rostral solitary nucleus.
abstract: 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.
authors.affiliation: Division of Oral Biology, College of Dentistry, The Ohio State University, Columbus, Ohio 43210, USA. alison.boxwell@osumc.edu
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Boxwell
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Susan P
authors.initials: SP
authors.lastname: Travers
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Travers
mesh_terms: D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D005071:Evoked Potentials; D059330:GABAergic Neurons / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D055369:Miniature Postsynaptic Potentials; D009433:Neural Inhibition; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
keywords: GABA; GAD67-GFP knockin mouse; disinhibition; taste