Direct excitatory opiate effects mediated by non-synaptic actions on rat medial vestibular neurons.
Opiates increase firing of rat medial vestibular nucleus neurons. We have attempted to determine the mechanism of these excitatory opiate actions by extracellular recording of neuronal activity with ionophoretic application of opiate agonists and bath application of antagonists. The spontaneous activity of approximately 30% of medial vestibular neurons, scattered throughout the nucleus, was increased by ionophoretic application of either morphine or [D-Ala2]leucine enkephalin, implicating the presence of both mu and delta opiate receptors. The responses to both were blocked by the opiate receptor antagonist, naloxone. In only a few neurons opiates decreased firing. Most previous reports of direct opiate excitation have proven to be due to disinhibition. This is not the case here, as indicated by three observations: 1) the excitatory opiate response was sustained when gamma-aminobutyric acid (GABA) receptors were blocked by bicuculline; 2) perfusion of a solution containing 0.1 mM Ca2+ and 6.3 mM Mg2+ blocks synaptic transmission, but does not block the excitatory responses to both opiates and 3) the opiate-induced depolarization and action potential generation was evident in neurons whose spontaneous firing was almost totally depressed by adenosine. These results indicate that the excitation is neither due to disinhibition nor to a presynaptic opiate action. We conclude that medial vestibular neurons have postsynaptic opiate receptors that mediate direct neuronal excitation.
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Wadsworth Center for Laboratories and Research, New York State Department of Health and School of Public Health, Albany 12201-0509.
Carpenter
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D007478:Iontophoresis; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014726:Vestibular Nuclei / Q000166:cytology / Q000187:drug effects*
D018079:Receptors, GABA; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D008274:Magnesium; D002118:Calcium; D001640:Bicuculline