MODULATION OF RAT-BRAIN CANNABINOID RECEPTORS AFTER CHRONIC MORPHINE TREATMENT

INTRAPERITONEAL injection of Delta(9)-THC (7.5 mg/kg) in rats made tol erant to morphine by s.c. implantation of morphine pellets had a much greater analgesic effect than in placebo pellet plus Delta(9)-THC trea tment. To investigate whether this was due to some change in cannabino id receptor levels and/or expression induced by chronic morphine, we d esigned this autoradiographic binding study coupled with in situ hybri dization an sagittal sections of the treated rat brains. Binding showe d a significant increase in CB1 receptor density (15%) specifically in the caudate-putamen, in parallel with a significant enhancement of CB 1 mRNA in the same area (20%). We suggest that morphine chronic treatm ent leads to a functional modulation between the opioid and cannabinoi d systems at least for analgesia in a specific area, in this case the striatum.