Endogenous opioids modulate neuronal survival in the developing avian ciliary ganglion.
Most studies on the trophic regulation of the normal neuronal competition for survival have focused on interactions between neurons and their target environment. However, it is also likely that trophic modulators are released from premotor inputs onto motoneurons. We have examined the developmental distribution of endogenous enkephalin-like immunoreactivity and the role that these endogenous opioid peptides play in normal neuronal degeneration. During the early portion of the normal cell death period, enkephalin-like immunoreactivity is highest within preganglionic cell bodies in the midbrain and their nerve terminals in the ciliary ganglion. Exogenous daily morphine administration to the chick embryo has previously been shown to delay most of the normal neuronal death in the ciliary ganglion (see Meriney et al., 1985). We hypothesized that opiate receptor activation increases the probability that ciliary ganglion neurons will survive their developmental competition and, further, that the endogenous opioid peptides in the ciliary ganglion normally modulate this competition. However, in our previous report (Meriney et al., 1985), we noted that daily administration of the antagonist naloxone to the chorioallantoic membrane did not significantly alter neuronal survival, as would have been expected if endogenous opioids were involved in regulating cell death. In contrast, in this report we show that three times daily application of naltrexone (a long-lasting opiate antagonist) significantly decreased neuronal survival among the ciliary ganglion cells, and that the surviving cells were not ultrastructurally different than neurons from controls of the same developmental stage. To control for toxic effects of naltrexone, we performed cell counts following naltrexone, we performed cell counts following naltrexone treatment in another population of cholinergic motoneurons (lumbar spinal motoneurons). In this population of cells, the total number of motoneurons remains unchanged following naltrexone treatment. To test for a specific toxic effect on the neurons of the ciliary ganglion, we generated a dose-response curve for toxicity in vitro and determined that naltrexone was not toxic over concentration ranges that are likely to exist in vivo. It appears, therefore, that a multiple daily antagonist application protocol blocks opiate receptors sufficiently in the ciliary ganglion to decrease an endogenous opiate influence significantly. We tested the possibility that endogenous opioids exert their effect by modifying transmission at peripheral and ganglionic synapses. In the generally accepted hypothesis, paralysis at the peripheral nerve-striated muscle synapse would rescue cells, while paralysis of ganglionic synapses would decrease survival. Iris neuromuscular junctions onto striated muscle cells were not blocked by opioids, but neuromuscular transmission in the smooth muscle of the choroid coat was blocked.(ABSTRACT TRUNCATED AT 400 WORDS)
Meriney
S D
SD
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269.
Ford
M J
MJ
Oliva
D
D
Pilar
G
G
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens / Q000502:physiology; D005314:Embryonic and Fetal Development; D004723:Endorphins / Q000502:physiology*; D004743:Enkephalin, Leucine / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000378:metabolism / Q000502:physiology*; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009410:Nerve Degeneration / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission
D004723:Endorphins; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine