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 reinforcing effects in rhesus monkeys and its phencyclidine (PCP)-like discriminative stimulus effects in rats. The monkeys were trained to self-administer PCP i.v. under a fixed ratio 10 schedule of reinforcement. After the monkeys were trained, saline, vehicle and various doses of eliprodil were substituted for PCP. The rats were trained to discriminate 3 micrograms/kg PCP from saline using a standard two-lever discrimination procedure with correct-lever responding reinforced under a fixed ratio 10 schedule of food reinforcement. After acquiring the discrimination, the rats were tested with various doses of PCP, dizocilpine and eliprodil. The self-administration study showed that eliprodil did not have reinforcing 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 studies suggest that eliprodil has a low potential for abuse in humans as well as providing further evidence that eliprodil produces a profile of behavioral effects unlike the PCP-site selective NMDA antagonists.
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0310.
R L
RL
Balster
K L
KL
Nicholson
D J
DJ
Sanger
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D009042:Motivation; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010622:Phencyclidine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration
D010880:Piperidines; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D010622:Phencyclidine; C058083:eliprodil