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Dose‐dependent effects of morphine (MOR) applied directly onto canine respiratory bulbospinal neurons
Author(s) -
Sanchez Antonio,
Zuperku Edward J.,
Stucke Astrid G.,
Hopp Francis A.,
Stuth Eckehard A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a560-a
Subject(s) - respiratory system , morphine , anesthesia , neuron , chemistry , premovement neuronal activity , respiratory rate , medicine , neuroscience , biology , heart rate , blood pressure
MOR is an effective analgesic with a limited clinical therapeutic range due to a profound depression of respiratory rate and drive. It is uncertain where in the respiratory control network its depressive effects take place. Respiratory bulbospinal (BS) neurons, which transmit phasic drive to motoneurons of the pump musculature, may be a key target. Thus, we studied the direct effects of MOR on single BS I and E neurons via picoejection in a decerebrate, vagotomized, paralyzed, and mechanically ventilated dog model. Four‐barrel glass micropipettes were used to record extracellular neuronal activity and eject 10 μM, 100 μM and 1000 μM MOR onto the neurons. MOR‐induced reductions in peak and average discharge frequency (F n ) and changes in discharge patterns were analyzed. Dose‐dependent effects (mean & SE) relative to control are given in the table for maximum effective dose‐rates, which approach barrel concentrations for electrode tip‐to‐neuron distances <200 μm. These results show that I and E BS neurons are depressed ~20% by 10 μM morphine. Since plasma concentrations of 20–50 ng/ml (26–66 nM) produce analgesia in dogs, direct morphine depression of BS neurons via neuronal μ‐receptors appears minimal at therapeutic doses. Supt: VA Med. Res. Funds & NIH GM59234.