Many problems implicated in the etiology of SIDS can be related to an imbalance in the body's own opioid system. Beta endorphin has been shown to be involved in respiratory control, hormone regulation and can affect the immune response. We have collected brainstem samples and cerebrospinal fluid (CSF) from approximately 32 cases of SIDS in the Salt Lake Valley. We are also developing an animal model (morphine treatment of pregnant rats to test the hypothesis that abnormally high levels of maternal endorphins act to produce a reduction in fetal endorphin levels and opioid receptors ( the incidence of SIDS increases dramatically in the population of pregnant women who abuse opiates during their pregnancies). After birth, there is a concomitant rebound in the number of opioid receptors and endorphin synthesis in the infant. Increased opioid receptor density in the brainstem respiratory centers coupled with an increase in endorphin synthesis or release could contribute to the fatal SIDS event. Results from our preliminary experiments indicate that in adult animals exposed to opioids there is a tremendous receptor rebound (supersensitivity) which develops after removal of the drug. In the present study, opioid receptors in the brains of pups from morphine-treated dams will be analyzed using quantitative techniques of receptor autoradiography. This state-of-the-art technology will allow us to examine the density and distribution of opioid receptors in individual brain regions. Mu opioid receptors (thought to be involved in the respiratory actions of opioids) will be quantitated in individual brainstem areas by comparison with (125I)-standards. Individual nuclei will be scrutinized by Scatchard analysis to determine if a change in receptor number or affinity has occured. Further evidence to support the hypothesis of the involvement of opioid receptor supersensitivity in the etiology of SIDS will be acquired by using computer-assisted microdensitometric techniques to analyze the actual number and affinity of receptors in human postmortem cases of SIDS. Successful completion of this study could implicate a role for the endogenous opioid system and the development of supersensitive opioid receptors in the etiology of SIDS. The experiments will demonstrate a possible pathogenesis of the disease and implicate opioid receptor antagonists as potential therapeutic agents which could be used to treat periodic apnea seen in high risk SIDS infants.
| Zarbin, M A; Wamsley, J K; Kuhar, M J (1990) Anterograde transport of opioid receptors in rat vagus nerves and dorsal roots of spinal nerves: pharmacology and sensitivity to sodium and guanine nucleotides. Exp Brain Res 81:267-78 |
| Kerr, L M; Filloux, F; Olivera, B M et al. (1988) Autoradiographic localization of calcium channels with [125I]omega-conotoxin in rat brain. Eur J Pharmacol 146:181-3 |
| McCabe, R T; Olsen, R W; Yezuita, J P et al. (1988) Osmotic shock: a method to eliminate endogenous gamma-aminobutyric acid and account for the influence on benzodiazepine binding affinity in autoradiographic studies. J Pharmacol Exp Ther 245:342-9 |
