Accelerated release and production of orphanin FQ in brain of chronic morphine tolerant rats.

Orphanin FQ has been shown to possess anti-opioid activity at supraspinal level. Our previous work revealed that chronic morphine tolerance could be reversed by intracerebroventricular (i.c.v.) injection of OFQ IgG to rats. In this study, we used radioimmunoassay (RIA) to assess the changes of Orphanin FQ immunoreactivity (OFQ-ir) in cerebroventricular perfusate, periaqueductal gray (PAG) and amygdala of rats made tolerance to morphine (10-60 mg/kg, s.c., t.i.d., for 5 days). The results indicated that: (1) In rats administrated with morphine for 3 and 5 days, the content of OFQ-ir in cerebroventricular perfusate increased by 25% and 52% over the NS control group. (2) The content of OFQ-ir in PAG of rats receiving 1d, 3d and 5d injections of morphine showed an increase of 17%, 48% and 81% respectively over NS group. (3) The content of OFQ-ir in amygdala of rats given 3d and 5d of morphine showed a 36% and 55% increase compared with corresponding control group. It is suggested that continuous use of high doses of morphine accelerated the release and biosynthesis of OFQ in rat brain to antagonize the effect of opioids, which may play a role in the development of morphine tolerance, and that brain OFQ may serve as a delayed negative feedback control on opioid analgesia.