Abstract
Directly observable behavioral effects of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP5) (10–1,000 mg/kg IP, 0.18–5.6 μmol/rat ICV) and of phencyclidine (PCP) (3.2–56 mg/kg IP, 0.032–3.2 mg/rat ICV), ketamine (10–100 mg/kg), amphetamine (1–18 mg/kg), apomorphine (0.1–5.6 mg/kg), chlordiazepoxide (1–100 mg/kg), and pentobarbital (3.2–56 mg/kg) were studied in rats. Pharmacologically specific results were obtained rapidly and reliably, using a cumulative dosing procedure. Cluster analysis grouped the drug treatments, on the basis of their similarities in producing different behavioral activities, into three main clusters; characteristically, stimulant drugs (amphetamine, apomorphine) produced sniffing and gnawing; PCP-like drugs (PCP, ketamine) produced locomotion, sniffing, swaying and falling; sedative drugs (pentobarbital, chlordiazepoxide) produced loss of righting. The behavioral effects of ICV administration of AP5 were more similar to the effects of PCP-like drugs than to the effects of either stimulant or sedative drugs, thus supporting the hypothesis that the behavioral effects of PCP-like drugs may result from reduced neurotransmission at excitatory synapses utilizing NMDA preferring receptors. The present procedure is simple, rapid and may provide a useful approach in the classification of behaviorally active drugs.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aldenderfer MS, Blashfield RK (1984) Cluster analysis. Sage university paper series on quantitative applications in the social sciences, 07-044. Sage, Beverly Hills
Bennett DA, Corradi CL, Lehmann J (1985) The excitatory amino acid receptor antagonist, 2-amino-7-phosphonoheptanoic acid (AP7), produces anticonflict activity. Soc Neurosci Abstr 11:106
Bennett DA, Amrick CL (1986) 2-Amino-7-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam. Life Sci 39:2455–2462
Chen G, Ensor CR, Russell D, Bohner B (1959) The pharmacology of 1-(1-phenylcyclohexyl)piperidine. HCl. J Pharmacol Exp Ther 127:241–250
Cook L, Davidson AB (1973) Effects of behaviorally active drugs in a conflict-punishment procedure in rats. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven, New York, pp 327–345
Dawbarn D, Pycock CJ (1981) Motor effects following application of putative excitatory amino acid antagonists to the region of the mesencephalic dopamine cell bodies in the rat. Naunyn-Schmiedeberg's Arch Pharmacol 318:100–104
Fray PJ, Sahakian BJ, Robbins TW, Koob GF, Iversen SD (1980) An observational method for quantifying the behavioural effects of dopamine agonists: contrasting effects of d-amphetamine and apomorphine. Psychopharmacology 69:253–259
Gordon AD (1981) Classification. Chapman and Hall, New York
Greenberg BD, Segal DS (1986) Evidence for multiple opiate receptor involvement in different phencyclidine-induced unconditioned behaviors in rats. Psychopharmacology 88:44–53
Iwamoto ET (1984) An assessment of the spontaneous activity of rats administered morphine, phencyclidine, or nicotine using automated and observational methods. Psychopharmacology 84:374–382
Koek W, Kleer E, Mudar PJ, Woods JH (1986a) Phencyclidine-like catalepsy induced by the excitatory amino acid antagonist DL-2-amino-5-phosphonovalerate. Behav Brain Res 19:257–259
Koek W, Woods JH, Ornstein P (1986b) Phencyclidine-like behavioral effects in pigeons induced by systemic administration of the excitatory amino acid antagonist, 2-amino-5-phosphonovalerate. Life Sci 39:973–978
Kullback S (1968) Information theory and statistics. Dover, New York
Leach C (1979) Introduction to statistics. Wiley, New York
Mudar P, Koek W, Jacobson AE, Woods JH (1986) Catalepsy in pigeons induced by excitatory amino acid receptor antagonists. Fed Proc 45:663
Robbins TW (1977) A critique of the methods available for the measurement of spontaneous motor activity. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology, vol 7. Plenum, New York, pp 37–82
Schiorring E (1971) Amphetamine-induced selective stimulation of certain behaviour items with concurrent inhibition of others in an open-field test with rats. Behaviour 39:1–17
Slifer BL, Balster RL (1985) A comparison of the discriminative stimulus properties of phencyclidine, given intraperitoneally or intraventricularly in rats. Neuropharmacology 24:1175–1179
Sturgeon RD, Fessler RG, Meltzer HY (1979) Behavioral rating scales for assessing phencyclidine-induced locomotor activity, stereotyped behavior and ataxia in rats. Eur J Pharmacol 59:169–179
Thompson T, Boren JJ (1977) Operant behavioral pharmacology. In: Honig WK, Staddon JER (eds) Handbook of operant behavior. Prentice-Hall, New Jersey, pp 540–569
Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 21:165–204
Willetts J, Chapman MY, Balster RL (1986) Discriminative stimulus effects of 2-amino-7-phosphonoheptanoic acid (APH) in phencyclidine-trained rats. Soc Neurosci Abstr 12:909
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Koek, W., Woods, J.H. & Ornstein, P. A simple and rapid method for assessing similarities among directly observable behavioral effects of drugs: PCP-like effects of 2-amino-5-phosphonovalerate in rats. Psychopharmacology 91, 297–304 (1987). https://doi.org/10.1007/BF00518181
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00518181