The appearance of endogenous opiates in cerebrospinal fluid following opiate injection in various animal species.

Phenylquinone writhing, tail-flick, stimulated guinea pig ileum and mouse vas deferens were used to quantitate opiate-like activity in CSF taken prior to and at various times after the injection of morphine. The injection of various doses of morphine caused a dose responsive increase in opiate-like material in rabbit CSF taken at the peak of activity (60 min later). Morphine also caused an increase in opiate activity in dog CSF. Quantitation of radioactivity in CSF after the injection of radiolabelled morphine, stability studies and other assays were used to rule out the possibility that the increased activity in CSF was due to morphine itself. CSF taken after morphine injection produced a peak on HPLC with a 15 minute retention time which was not present in CSF taken prior to the injection. This peak was not caused by morphine, met-enkephalin, leu-enkephalin, dynorphin 1-13 or beta-endorphin which have retention times of 5, 7, 9, 22 and 30 minutes, respectively. Preinjection of the rabbit with naloxone blocked the increased opiate-like effects of CSF taken after morphine and the opiate effects of the CSF were antagonized by naloxone injected into mice or the isolated organ bath.