The discriminative stimulus effects of N-methyl-D-aspartate antagonists in phencyclidine-trained rats

Neuropharmacology. 1988 Dec;27(12):1249-56. doi: 10.1016/0028-3908(88)90027-5.


The discriminative stimulus effects of two competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-7-phosphonoheptanoate (APH) and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonate (CPP), were assessed in rats trained to discriminate phencyclidine from saline. Systemically administered APH (10-60 mg/kg i.p.) failed to elicit phencyclidine-lever responding; however, partial generalization from phencyclidine occurred following intracerebroventricular (i.c.v.) administration of APH (1.5-30 micrograms). Systemic and central administration of CPP (3-30 mg/kg i.p.; 0.1-10 micrograms i.c.v.) also resulted in partial generalization from phencyclidine. Partial generalization was also obtained with methohexital (5-30 mg/kg i.p.). However, generalization to APH, CPP and methohexital was usually accompanied by decreased response rates, and response rate decreases frequently occurred without appreciable phencyclidine-lever selection, indicating that these drugs also had no phencyclidine-like behavioral effects. The drug di-ortho-tolyl guanidine (DTG) which binds with high-affinity to sigma receptors failed to elicit phencyclidine-lever responding, even at doses which reduced response rates. These findings suggest that although competitive NMDA antagonists share some discriminative stimulus properties with phencyclidine, there is not a complete overlap in the discriminative stimulus properties of competitive and non-competitive NMDA antagonists. Furthermore, the discriminative stimulus effects of APH and CPP were no more similar to phencyclidine than those of methohexital.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate* / analogs & derivatives*
  • Amino Acids / pharmacology*
  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / antagonists & inhibitors
  • Discrimination, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Injections, Intraventricular
  • Male
  • Methohexital / pharmacology
  • N-Methylaspartate
  • Phencyclidine*
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Time Factors


  • Amino Acids
  • Piperazines
  • Aspartic Acid
  • N-Methylaspartate
  • 2-Amino-5-phosphonovalerate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Methohexital
  • Phencyclidine
  • 2-amino-7-phosphonoheptanoic acid