EVALUATION OF THE REINFORCING EFFECTS OF ELIPRODIL IN RHESUS-MONKEYS AND ITS DISCRIMINATIVE STIMULUS EFFECTS IN RATS

Two studies examined the abuse potential of the N-methyl-D-aspartate ( NMDA) non-competitive antagonist eliprodil alpha-(4-chlorophenyl)-4-[( fluorophenyl)methyl]-1- piperidineethanol] by evaluating its reinforci ng effects in rhesus monkeys and its phencyclidine (PCP)-like discrimi native stimulus effects in rats. The monkeys were trained to self-admi nister PCP i.v. under a fixed ratio 10 schedule of reinforcement. Afte r the monkeys were trained, saline, vehicle and various doses of elipr odil were substituted for PCP. The rats were trained to discriminate 3 mu g/kg PCP from saline using a standard two-lever discrimination pro cedure with correct-lever responding reinforced under a fixed ratio 10 schedule of food reinforcement. After acquiring the discrimination, t he rats were tested with various doses of PCP, dizocilpine and eliprod il. The self-administration study showed that eliprodil did not have r einforcing effects, since it maintained injection rates comparable to the negative controls, saline and vehicle. In the discrimination study it was found that the higher doses of PCP and dizocilpine resulted in 100% PCP-associated lever responding, whereas eliprodil occasioned no responding on the PCP-associated lever. The results from these studie s suggest that eliprodil has a low potential for abuse in humans as we ll as providing further evidence that eliprodil produces a profile of behavioral effects unlike the PCP-site selective NMDA antagonists.