REINFORCING PROPERTIES OF STEREOISOMERS OF THE PUTATIVE SIGMA-AGONISTS N-ALLYLNORMETAZOCINE AND CYCLAZOCINE IN RHESUS-MONKEYS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 225  (3) , 522-528
Abstract
There are many similarities in the effects of phencyclidine (PCP) and opioids with .sigma.-agonist activity such as N-allylnormetazocine (SKF-10,047) and cyclazocine. Yet PCP and .sigma.-agonists differ in reinforcing properties. PCP is reliablly self-administered in animal models and has abuse liability in humans, whereas (.+-.)-N-allylnormetazocine and (.+-.)-cyclazocine are not self-administered or abused. Inasmuch as other research has demonstrated differences in the selectivity of PCP-like effects of the stereoisomers of opioids, this study compared the reinforcing properties of PCP to the reinforcing properties of isomers of N-allylnormetazocine and cyclazocine. Rhesus monkeys were trained to level-press on a fixed-ratio 10 schedule for i.v. cocaine (50 .mu.g/kg per injection). During substitution tests, cocaine was replaced with various doses of test drugs or vehicle. The drugs tested were PCP, (.+-.)-N-allylnormetazocine, (.sbd.)-N-allynormetazocine, (+)-N-allylnormetazocine, (.+-.)-cyclazocine, (-)-cyclazocine and (+)-cyclazocine. PCP and the (+)-isomers of both benzomorphans, at one or more doses, were self-administered at rates which exceeded rates maintained by vehicle and which equaled or exceeded cocaine-maintained base-line rates. Neither the racemates nor the (.sbd.)-isomers of N-allylnormetazocine or cyclazocine were self-administered by the monkeys at rates which were greater than vehicle control levels of responding. Reinforcing doses of the 3 compounds resulted in injections evenly distributed across the 60-min session in a pattern similar to cocaine self-administration, whereas the racemic mixtures and the (.sbd.)-isomers produced negatively accelerated patterns of injections which resembled typical saline patterns of extinction responding. The (+)-isomers of .sigma.-agonists are evidently more selective for PCP-like effects than the (.sbd.)-isomers in monkeys.