Abstract
Pigeons were trained to discriminate either a fixed dose of PCP (1 mg/kg; n=3) or a progressively decreasing dose (1-0.56–0.32 mg/kg; n=4) from saline. Lowering of the training dose shifted the dose-effect curve for PCP's discriminative stimulus effects about 5-fold to the left, in a parallel manner, but did not decrease the accuracy of the discrimination performance and did not significantly increase the extent to which pentobarbital and chlordiazepoxide produced PCP-appropriate responding. Dose-effect curves based on binary generalization data were evaluated statistically with new methods that may be more appropriate than those used previously. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an N-methyl-d-aspartate (NMDA) antagonist, produced complete PCP-appropriate responding in the high training dose group only at doses that suppressed the rate of responding and that produced ataxia. However, 4-fold lower doses of metaphit and AP5, which did not produce directly observable behavioral effects, were found to substitute completely for PCP in the low training dose group. These data support the notion that PCP, metaphit, and AP5 have a common discriminative effect in pigeons.
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References
Beardsley PM, Balster RL, Salay JM (1987) Separation of the response rate and discriminative stimulus effects of phencyclidine: training dose as a factor in phencyclidine-saline discrimination. J Pharmacol Exp Ther 241:159–165
Bennett DA, Corradi CL, Lehman CJ (1985) The excitatory amino acid receptor antagonist, 2-amino-7-phosphonoheptanoic acid (AP7) produces anticonflict activity. Soc Neurosc (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 (in press)
Chen GM, Weston JK (1960) The analgesic and anesthetic effect of 1-(1-phenylcyclohexyl)piperidine HCl on the monkey. Anesth Analg 39:132–137
Chen GM, Ensor CR, Russell D, Bohner B (1959) The pharmacology of 1-(1-phenylcyclohexyl)piperidine HCl. J Pharmacol Exp Ther 127:241–250
Colpaert FC (1986) Drug discrimination: methods of manipulation, measurement and analysis. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs (in press)
Colpaert FC, Niemegeers CJE, Janssen PAJ (1980) Factors regulating drug cue sensitivity: the effect of training dose in fentanylsaline discrimination. Neuropharmacology 19:705–713
Contreras PC, Johnson S, Freedman R, Hoffer B, Olsen K, Rafferty MF, Lessor RA, Rice KC, Jacobson AE, O'Donohue TL (1986) Metaphit, an acylating ligand for phencyclidine receptors: characterization of in vivo actions in the rat. J Pharmacol Exp Ther 238:1101–1107
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
Domino EF, Luby ED (1981) Abnormal mental states induced by phencyclidine as a model of schizophrenia. In: EF Domino (ed) PCP (phencyclidine): historical and current perspectives. NPP Books, Ann Arbor, pp 401–418
Everitt BS (1977) The analysis of contingency tables. Chapman and Hall, London
Fagg GE, Foster AC, Ganong AH (1986) Excitatory amino acid synaptic mechanisms and neurological function. TIPS 7:357–363
Herling S, Coale EH Jr, Hein DW, Winger G, Woods JH (1981) Similarity of the discriminative stimulus effects of ketamine, cyclazocine, and dextrorphan in the pigeon. Psychopharmacology 73:286–291
Koek W, Head R, Holsztynska EJ, Woods JH, Domino EF, Jacobson AE, Rafferty MF, Rice KC, Lessor RA (1985) Effects of metaphit, a proposed phencyclidine receptor acylator, on catalepsy in pigeons. J Pharmacol Exp Ther 234:648–653
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
Koek W, Woods JH, Jacobson AE, Rice KC, Lessor RA (1986c) Metaphit, a proposed phencyclidine receptor acylator: phencyclidine-like behavioral effects and evidence of absence of antagonist activity in pigeons and in rhesus monkeys. J Pharmacol Exp Ther 237:386–392
Koek W, Woods JH, Ornstein P (1987) 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
Leander JD (1982) Comparison of phencyclidine, etoxadrol and dexoxadrol in the pigeon. Subst Alcohol Actions Misuse 2:197–203
Litchfield JT, Wilcoxon FJ (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113
McMillan DE (1982) Generalization of the discriminative stimulus properties of phencyclidine to other drugs in the pigeon using color tracking under second order schedules. Psychopharmacology 78:131–134
McMillan DE, Wenger GR (1983) Effects of barbiturates and other sedative hypnotics in pigeons trained to discriminate phencyclidine from saline. J Exp Anal Behav 40:133–142
Meldrum B (1985) Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. Clin Sci 68:113–122
Overton DA (1974) Experimental methods for the study of state-dependent learning. Fed Proc 33:1800–1813
Overton DA (1975) A comparison of the discriminable CNS effects of ketamine, phencyclidine and pentobarbital. Arch Int Pharmacodyn Ther 215:180–189
Overton DA (1984) State dependent learning and drug discriminations. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 18. Plenum, New York, pp 59–127
Rafferty MF, Mattson M, Jacobson AE, Rice KC (1985) A specific acylating agent for the [3H]phencyclidine receptors in rat brain. FEBS Lett 181:318–322
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
Stephens DN, Meldrum BS, Weidmann R, Schneider C, Grutzner M (1986) Does the excitatory amino acid receptor antagonist 2-APH exhibit anxiolytic activity? Psychopharmacology 90:166–169
Stolerman IP, D'Mello GD (1981) Role of training conditions in discrimination of central nervous system stimulants in rats. Psychopharmacology 73:295–303
Tallarida RJ, Murray RB (1981) Manual of pharmacologic calculations. Springer, New York Berlin Heidelberg
Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 21:165–204
Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York
Woods JH, Koek W, Ornstein P (1987) A preliminary study of PCP-like behavioral effects of 2-amino-5-phosphonovalerate in rhesus monkeys. In: Hicks TP, Lodge D, McLellan H (eds) Excitatory amino acid transmission. Liss, New York, pp 205–212
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Koek, W., Woods, J.H., Jacobson, A.E. et al. Phencyclidine (PCP)-like discriminative stimulus effects of metaphit and of 2-amino-5-phosphonovalerate in pigeons: generality across different training doses of PCP. Psychopharmacology 93, 437–442 (1987). https://doi.org/10.1007/BF00207232
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DOI: https://doi.org/10.1007/BF00207232