Evaluation of the reinforcing effects of eliprodil in rhesus monkeys and its discriminative stimulus effects in rats. 1994

R L Balster, and K L Nicholson, and D J Sanger
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0310.

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.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D008297 Male Males
D009042 Motivation Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli. Incentives,Disincentives,Expectations,Disincentive,Expectation,Incentive,Motivations
D010622 Phencyclidine A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust. 1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D010880 Piperidines A family of hexahydropyridines.
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004193 Discrimination Learning Learning that is manifested in the ability to respond differentially to various stimuli. Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response

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