Morphine-6-glucuronide contributes to rewarding effects of opiates

It was recently confirmed that a metabolite of morphine, morphine-6-glucuronide (M6G), is a long lasting, powerful analgesic in humans and animals and may account for a major component of clinical opiate analgesia. It is reported here that M6G is also a powerful behavioral reinforcer in the conditioned place preference test in rats, indicating that it has rewarding properties, and is therefore likely to have abuse potential. The induction of a place preference by M6G is blocked by naltrexone, indicating that the rewarding effect of M6G is mediated by opioid receptors. Given systemically M6G is approximately equipotent with morphine. When given intracerebroventricularly to bypass the blood-brain barrier, M6G is 146 times more potent than morphine in the place preference test. Thus 6-substituted metabolites of opiates may play a more significant role in the effects of opiates than has been previously assumed.