Biomaterial Database

Phencyclidine-like discriminative stimulus effects of polyamine modulators of N-methyl-D-aspartate receptor activity in rats. 1998

K L Nicholson, and R L Balster

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613, USA.

Excessive N-methyl-D-aspartate (NMDA) receptor activation has been implicated in many acute and chronic neuropathologies. NMDA antagonists might prove to be useful treatments, unfortunately, some can produce phencyclidine (PCP)-like side effects. The polyamine-site modulators, spermine (SPM) and spermidine (SPD), produce dose related biphasic modulation of NMDA channel currents while another polyamine, arcaine (ARC), produces only negative modulatory effects. The PCP-like effects of these compounds were tested in rats trained to discriminate PCP from saline in a standard two-lever drug discrimination paradigm under a fixed ratio schedule of food reinforcement. SPM, SPD and ARC occasioned little, if any, responding on the PCP-associated lever, even at response rate suppressing doses. The results provide further evidence that differences exist between the discriminative stimulus effects produced by drugs active at different sites on the NMDA receptor and suggest that the polyamine modulatory site should be a good target for development of NMDA antagonist medications with a reduced propensity for PCP-like acute behavioral effects.

UI	MeSH Term	Description	Entries
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
D012054	Reinforcement, Psychology	The strengthening of a conditioned response.	Negative Reinforcement,Positive Reinforcement,Psychological Reinforcement,Reinforcement (Psychology),Negative Reinforcements,Positive Reinforcements,Psychological Reinforcements,Psychology Reinforcement,Psychology Reinforcements,Reinforcement, Negative,Reinforcement, Positive,Reinforcement, Psychological,Reinforcements (Psychology),Reinforcements, Negative,Reinforcements, Positive,Reinforcements, Psychological,Reinforcements, Psychology
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001645	Biguanides	Derivatives of biguanide (the structure formula HN(C(NH)NH2)2) that are primarily used as oral HYPOGLYCEMIC AGENTS for the treatment of DIABETES MELLITUS, TYPE 2 and PREDIABETES.	Biguanide
D013095	Spermidine	A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.
D013096	Spermine	A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure.
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate