Chronic treatment of newborn rats with naltrexone alters astrocyte production of nerve growth factor.
Newborn rats were treated with the opiate antagonist naltrexone daily for 1-2 wk in order to examine the effects of endogenous opioid peptides on astrocytes during CNS development. Nerve growth factor (NGF) and cyclic AMP were measured in astrocytes cultured from cerebellum, striatum, and hippocampus of 1 d, 1 wk, and 2 wk postnatal rats. Cerebellar and striatal, but not hippocampal, astrocytes prepared from naltrexone-treated animals produced higher levels of NGF than those from controls. The turnover rate of cyclic AMP, measured following treatment of the cells with forskolin in the presence of the phosphodiesterase inhibitor IBMX, was increased in naltrexone-derived cerebellar and striatal astrocytes. Opiate receptors could not be detected on the cultured astrocytes, either by direct binding of 3H-etorphine or by modulation of cyclic AMP content. These results suggest that endogenous opioid peptides may function indirectly to alter trophic factor synthesis in astrocytes.
Mitsuo
K
K
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Schwartz
J P
JP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000254:growth & development; D011957:Receptors, Opioid / Q000032:analysis
D009414:Nerve Growth Factors; D011957:Receptors, Opioid; D005576:Colforsin; D009271:Naltrexone; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine