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Evaluation of the reinforcing and discriminative stimulus effects of the N-methyl-D-aspartate competitive antagonist NPC 17742 in rhesus monkeys.
Behav Pharmacol. 1997 Oct; 8(5):396-407.BP

Abstract

The phencyclidine (PCP)-like effects of the N-methyl-D-aspartate (NMDA) competitive antagonist 2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 17742) were evaluated in three behavioral tests in rhesus monkeys. The discriminative stimulus properties of NPC 17742 (2-24 mg/kg, i.m.) were tested in four rhesus monkeys trained to discriminate PCP from saline under a fixed-ratio (FR) 50 schedule of food reinforcement. In three of the monkeys, NPC 17742 showed complete substitution for PCP at doses which did not decrease rates of responding. Intravenous self-administration of NPC 17742 (50-800 micrograms/kg/infusion) was tested under a FR schedule of reinforcement in four monkeys trained to lever press for infusions of PCP. At least one dose of NPC 17742 functioned as a reinforcer in two of the monkeys. A second self-administration study, employing a 10 min fixed interval schedule of reinforcement, was performed in three monkeys trained to self-administer PCP during three daily sessions. Compared with PCP, NPC 17742 (0.4-1.6 mg/kg/infusion) maintained very low rates of responding; NPC 17742 could not be clearly established as a reinforcer in this procedure. The data show that NPC 17742 has some PCP-like behavioral effects, and may function as a weak reinforcer in some subjects under specific conditions. The results provide further evidence that both similarities and differences exist between the behavioral effects of PCP and competitive NMDA antagonists.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0310, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9832979

Citation

Nicholson, K L., et al. "Evaluation of the Reinforcing and Discriminative Stimulus Effects of the N-methyl-D-aspartate Competitive Antagonist NPC 17742 in Rhesus Monkeys." Behavioural Pharmacology, vol. 8, no. 5, 1997, pp. 396-407.
Nicholson KL, Jones HE, Balster RL. Evaluation of the reinforcing and discriminative stimulus effects of the N-methyl-D-aspartate competitive antagonist NPC 17742 in rhesus monkeys. Behav Pharmacol. 1997;8(5):396-407.
Nicholson, K. L., Jones, H. E., & Balster, R. L. (1997). Evaluation of the reinforcing and discriminative stimulus effects of the N-methyl-D-aspartate competitive antagonist NPC 17742 in rhesus monkeys. Behavioural Pharmacology, 8(5), 396-407.
Nicholson KL, Jones HE, Balster RL. Evaluation of the Reinforcing and Discriminative Stimulus Effects of the N-methyl-D-aspartate Competitive Antagonist NPC 17742 in Rhesus Monkeys. Behav Pharmacol. 1997;8(5):396-407. PubMed PMID: 9832979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the reinforcing and discriminative stimulus effects of the N-methyl-D-aspartate competitive antagonist NPC 17742 in rhesus monkeys. AU - Nicholson,K L, AU - Jones,H E, AU - Balster,R L, PY - 1998/12/2/pubmed PY - 1998/12/2/medline PY - 1998/12/2/entrez SP - 396 EP - 407 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 8 IS - 5 N2 - The phencyclidine (PCP)-like effects of the N-methyl-D-aspartate (NMDA) competitive antagonist 2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 17742) were evaluated in three behavioral tests in rhesus monkeys. The discriminative stimulus properties of NPC 17742 (2-24 mg/kg, i.m.) were tested in four rhesus monkeys trained to discriminate PCP from saline under a fixed-ratio (FR) 50 schedule of food reinforcement. In three of the monkeys, NPC 17742 showed complete substitution for PCP at doses which did not decrease rates of responding. Intravenous self-administration of NPC 17742 (50-800 micrograms/kg/infusion) was tested under a FR schedule of reinforcement in four monkeys trained to lever press for infusions of PCP. At least one dose of NPC 17742 functioned as a reinforcer in two of the monkeys. A second self-administration study, employing a 10 min fixed interval schedule of reinforcement, was performed in three monkeys trained to self-administer PCP during three daily sessions. Compared with PCP, NPC 17742 (0.4-1.6 mg/kg/infusion) maintained very low rates of responding; NPC 17742 could not be clearly established as a reinforcer in this procedure. The data show that NPC 17742 has some PCP-like behavioral effects, and may function as a weak reinforcer in some subjects under specific conditions. The results provide further evidence that both similarities and differences exist between the behavioral effects of PCP and competitive NMDA antagonists. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/9832979/Evaluation_of_the_reinforcing_and_discriminative_stimulus_effects_of_the_N_methyl_D_aspartate_competitive_antagonist_NPC_17742_in_rhesus_monkeys_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=9832979.ui DB - PRIME DP - Unbound Medicine ER -