Do kappa agonists increase the abuse-related effects of cocaine?
S. Stevens Negus. McLean Hospital, Harvard Medical School Kappa agonists have been reported to attenuate some neurochemical and behavioral effects of cocaine, and kappa agonists constitute one class of drugs being evaluated as potential pharmacotherapies for cocaine dependence. We have conducted an extensive series of studies to examine the effects of kappa agonists on the discriminative stimulus and reinforcing effects of cocaine in rhesus monkeys, and some of these studies will be reviewed. In drug discrimination studies, rhesus monkeys were trained to discriminate 0.4 mg/kg cocaine from saline. Under these conditions, acute pretreatment with the selective kappa agonist U50,488 produced highly variable but naloxone-reversible effects across monkeys, and leftward/upward shifts in the cocaine discrimination dose-effect curve were observed in most monkeys. In one set of drug self-administration studies, rhesus monkeys were trained to respond for cocaine injections or food pellets under
