Skip to main content
Log in

A rapid method for evaluating the behavioral effects of phencyclidine-like dissociative anesthetics in mice

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

A simple and rapid method for detecting the behavioral effects of phencyclidine and related dissociative anesthetics is described. Dissociative anesthetics such as phencyclidine (PCP) and dizolcipine, which bind with high affinities at N-methyl-D-aspartate (NMDA) coupled cation channels (“PCP receptors”), produced a dose-related increase in the percentage of mice that fell from a 1.5 cm deep circular arena mounted on a 60 cm platform. A similar behavior was not manifest by other classes of compounds examined including competitive NMDA antagonists, an antagonist at strychnine-insensitive glycine receptors, and σ-receptor ligands with moderate to low affinities for PCP receptors. Pretreatment of mice with glycine reduced in a dose-dependent manner the percentage of falls elicited by a maximally effective dose of dizolcipine. This simple procedure may prove useful for both the rapid detection of dissociative anesthetics and evaluation of putative PCP antagonists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Balster R (1980) The effects of phencyclidine and three analogues on motor performance in mice. Pharmacology 20:46–51

    CAS  PubMed  Google Scholar 

  • Bennett D, Amrick C (1986) 2-Amino-7-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam. Life Sci 39:2455–2461

    Article  CAS  PubMed  Google Scholar 

  • Choi D (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634

    Article  CAS  PubMed  Google Scholar 

  • Contreras P (1990)D-Serine antagonized phencyclidine and MK-801-induced stereotyped behavior and ataxia. Neuropharmacology 29:291–293

    Article  CAS  PubMed  Google Scholar 

  • Deutsch S, Mastropaolo J, Schwartz B, Rosse R, Morihisa J (1989) A “glutamatergic hypothesis” of schizophrenia. Clin Neuropharmacol 12:1–13

    CAS  PubMed  Google Scholar 

  • Goldman M, Jacobson A, Rice K, Paul S (1985) Differentiation of [3H]phencyclidine and (+)-[3H]SKF-10,047 binding sites in rat cerebral cortex. FEBS Lett 190:333–336

    CAS  PubMed  Google Scholar 

  • Jackson A, Sanger D (1988) Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-D-aspartate receptors? Psychopharmacology 96:87–92

    CAS  PubMed  Google Scholar 

  • Johnson K, Jones S (1990) Neuropharmacology of phencyclidine: basic mechanisms and therapeutic potential. Annu Rev Pharmacol Toxicol 30:707–750

    Article  CAS  PubMed  Google Scholar 

  • Keana J, Scherz M, Quarum M, Sonders M, Weber E (1988) Synthesis and characterization of a radiolabelled derivative of the phencyclidine/N-methyl-D-aspartate receptor ligand (+)MK-801 with high specific radioactivity. Life Sci 43:965–973

    Article  CAS  PubMed  Google Scholar 

  • Koek W, Woods J, Jacobsen A, Rice K (1987) Phencyclidine-like behavioral effects in pigeons induced by systemic administration of the excitatory amino acid antagonist, 2-amino-5-phosphonovalerate. Psychopharmacology 93:437–441

    Article  CAS  PubMed  Google Scholar 

  • Koek W, Woods J, Winger G (1988) MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys. J Pharmacol Exp Ther 245:969–974

    CAS  PubMed  Google Scholar 

  • Leander J, Wood C, Zimmerman D, dykstra L (1986) Phencyclidine-type catalepsy in the pigeon: an update on Chen's work. Drug Dev Res 7:75–85

    Article  CAS  Google Scholar 

  • Martin D, Lodge D (1988) Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviors. Pharmacol Biochem Behav 31:279–286

    Article  CAS  PubMed  Google Scholar 

  • Marwaha J, Palmer M, Hoffer B, Freedman R, Rice K, Paul S, Skolnick P (1981) Differential electrophysiological and behavioral responses to optically active derivatives of phencyclidine. Naunyn-Schmiedeberg's Arch Pharmacol 315:203–209

    Article  CAS  Google Scholar 

  • Mendelsohn L, Kerchner G, Kalra V, Zimmerman D, Leander D (1984) Phencyclidine receptors in rat cortex. Biochem Pharmacol 33:3529–3535

    Article  CAS  PubMed  Google Scholar 

  • Olney J (1989) Excitatory amino acids and neuropsychiatric disorders. Biol Psychiatry 26:505–525

    Article  CAS  PubMed  Google Scholar 

  • Rogawski M, Thurkauf A, Rice K, Jacobsen A, French-Mullen J (1988) Anticonvulsant activity of phencyclidine analogs: structural modifications resulting in enhanced seizure protection relative to motor side effect. In: Cavalheiro E, Lehmann J, Turdki L (eds) Frontiers in excitatory amino acid research. Liss, New York, pp 227–230

    Google Scholar 

  • Shannon H (1983) Discriminative stimulus effects of phencyclidine: structure-activity relationships. In: Kamenka J, Domino E, Geneste P (eds) Phencyclidine and related arylcyclohexylamines: present and future applications. NPP Books, Ann Arbor, pp 311–335

    Google Scholar 

  • Skolnick P, Marvizon J, Jackson B, Monn J, Rice K, Lewin A (1989) Blockade of N-methyl-D-aspartate induced convulsions by 1-aminocyclopropanecarboxylates. Life Sci 45:1647–1655

    Article  CAS  PubMed  Google Scholar 

  • Thurkauf A, Mattson M, Jacobson A, Rice K (1988) Synthesis of a molecular hybrid of phencyclidine and dexoxadrol. In: Domino E, Kamenka J (eds) Sigma and phencyclidine-like compounds as molecular probes in biology. NPP Books, Ann Arbor, pp 47–54

    Google Scholar 

  • Toth E (1988) Studies on the inhibition of phencyclidine-induced hyperactivity by glycine in mice. In: Domino E, Kamenka J (eds) Sigma and phencyclidine-like compounds as molecular probes in biology. NPP Books, Ann Arbor, pp 483–491

    Google Scholar 

  • Toth E, Lajtha A (1986) Antagonism of phencyclidine-induced hyperactivity by glycine in mice. Neurochem Res 11:393–400

    Article  CAS  PubMed  Google Scholar 

  • Tricklebank M, Singh L, Oles R, Wong E, Iversen S (1987) A role for receptors of N-methyl-D-aspartic acid in the discriminative stimulus properties of phencyclidine. Eur J Pharmacol 141:497–501

    Article  CAS  PubMed  Google Scholar 

  • Trullas R, Skolnick P (1990) Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 185:1–10

    Article  CAS  PubMed  Google Scholar 

  • Vincent J, Kartalovski B, Geneste P, Kamenka J, Lazdunski M (1979) Interaction of phencyclidine (“angel dust”) with a specific receptor in rat brain membranes. Proc Natl Acad Sci USA 76:4678–4682

    CAS  PubMed  Google Scholar 

  • Waziri R (1988) Glycine therapy of schizophrenia. Biol Psychiatry 23:209–214

    Article  Google Scholar 

  • Willetts J, Balster R (1988a) Phencyclidine-like discriminative stimulus properties of MK-801. Eur J Pharmacol 146:167–169

    CAS  PubMed  Google Scholar 

  • Willetts J, Balster R (1988b) The discriminative stimulus properties of N-methyl-D-aspartate antagonists in phencyclidine trained rats. Neuropharmacology 27:1249–1256

    Article  CAS  PubMed  Google Scholar 

  • Willetts J, Bobelis D, Balster R (1989) Drug discrimination based on the competitive N-methyl-D-aspartate antagonist, NPC 12626. Psychopharmacology 99:458–462

    Article  CAS  PubMed  Google Scholar 

  • Wong E, Kemp J, Priestley T, Knight A, Woodruff G, Iversen L (1986) The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. Proc Natl Acad Sci USA 83:7104–7108

    CAS  PubMed  Google Scholar 

  • Zukin S, Zukin R (1979) Specific [3H]phencyclidine binding sites in rat central nervous system. Proc Natl Acad Sci USA 76:5372–5376

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Evoniuk, G.E., Hertzman, R.P. & Skolnick, P. A rapid method for evaluating the behavioral effects of phencyclidine-like dissociative anesthetics in mice. Psychopharmacology 105, 125–128 (1991). https://doi.org/10.1007/BF02316874

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02316874

Key words

Navigation