(+)-N-Allylnormetazocine (NANM)-like discriminative stimulus effects of N-methyl-D-aspartate (NMDA) antagonists.
The effects of the competitive NMDA antagonists, 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) and 3-(2-carboxypiperazin-4-yl) propyl-l-phosphonic acid (CPP), were compared to those of the noncompetitive NMDA antagonists, phencyclidine (PCP) and (+)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d) cyclohepten-5, 10-imine maleate (MK-801), in male Sprague-Dawley rats trained to discriminate 5 mg/kg (+)-N-allyl-normetazocine (NANM) from saline under a standard two-lever fixed-ratio 32 schedule of food reinforcement. (+) - NANM, PCP and MK-801 dose-dependently substituted for the training dose of (+) - NANM in all rats tested. Conversely, NPC 12626 and CPP produced no more than an average of 73% (+) - NANM-lever responding at doses that also reduced response rates by more than 50% of corresponding control response rates. Methohexital also produced an average of 50% (+) - NANM-lever responding at doses that reduced response rates. In addition to supporting a role for the PCP receptor in transducing the discriminative stimulus effects of (+) - NANM, these results lend further evidence for differences in the behavioral effects of competitive and noncompetitive NMDA antagonists.
Willetts
J.
J
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298 USA Present addresses: J. Willetts, Harvard Medical School, New England Regional Primate Research Center, One Pine Hill Drive, Southborough, MA 01772, USA; A. Rice, Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA Correspondence to R.L. Balster, Department of Pharmacology and Toxicology, Box 613 MCV Station, Richmond, VA 23298-0613, USA.
Rice
A.
A
Balster
R.L.
RL