Prevention of cocaine-induced hyperactivity by a naloxone isomer with no opiate antagonist activity

Dextro-naloxone (+)-naloxone], an isomer with almost no opiate antagonist activity and no effect on spontaneous locomotor activity, can reduce cocaine-induced hyperactivity in mice. The classical opiate antagonist,levo-naloxone (−)-naloxone], is known to counteract the excitatory motor effects of amphetamine and cocaine, but it has been tacitly assumed that this action oflevo-naloxone is dependent on its ability to antagonize endogenous opioids. Our finding that a naloxone isomer with little or no opioid antagonist activity is also able to inhibit the cocaine effect on spontaneous motility, calls for a reconsideration of this assumption.