Opiate dependence and withdrawal

The model proposed by Snyder does not help to explain the paradox that few behavioral alterations are observed when naloxone is given to normal animals, since it would be predicted to cause withdrawal symptoms. This apparent discrepancy may be due to a differential mode of action of morphine and enkephalin at opiate receptors or to the existence of multiple categories of such receptors, as discussed above. There are certain opiates that are much weaker in competing for enkephalin than for naloxone and certain drugs that are about equipotent in this respect. In fact, it has been demonstrated that naloxone is relatively weak against enkephalin binding and potent against morphine binding. This may explain why it is more difficult to reverse the effects of endogenous enkephalin with naloxone than it is to reverse the effects of morphine and it could also explain the absence of naloxone-induced behavioral effects in the normal rat.