Abstract
The behavioral effects of single doses of phencyclidine (PCP) were examined in drug-naive adult male Holtzman rats trained to press a bar on a fixed ratio (4) schedule (FR4), i.e., a reward of sugarsweetened milk was earned on every fourth bar press. Groups of rats (four to eight rats per group) received specific doses of PCP which were held constant for each group throughout the study. Dose-response curves for PCP given in doses of 1.0, 1.8, 2.4, and 3.2 mg/kg IP were first determined and then redetermined at weekly intervals. A drug-free interval of 7–8 days was maintained between injections given weekly over a period of 4 weeks. The final dose of PCP was administered after a 4-week drug-free period. Evidence was obtained for first dose behavioral tolerance as shown by the significantly shortened duration of suppression of bar pressing on subsequent injections. Although subsequent weekly effects of equal doses of PCP showed no significant differences, they all differed significantly from the first injection. The reduced response to PCP was shown to be due to learned behavioral tolerance as demonstrated when PCP (3.2 mg/kg IP) was given to drug-naive animals in their home cages and 1 week later given the second dose in the operant behavioral situation. Under these circumstances, the second dose of PCP showed a similarly protracted depression of FR4 responding as other animals given the drug for the first time in the operant situation. Subsequent weekly injections in the operant situation produced similar behavioral tolerance.
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Burns, R. S., Lerner, S. E.: Phencyclidine: An emerging drug problem. Clin. Toxicol. 9, 477–501 (1976)
Burns, R. S., Lerner, S. E., Corrado, R., James, S. H., Schnoll, S. H.: Phencyclidine. States of acute intoxication and fatalities. West. J. Med. 123, 345–349 (1975)
Chait, L. D., Balster, R. L.: The effects of acute and chronic phencyclidine in schedule-controlled behavior in the squirrel monkey. J. Pharmacol. Exp. Ther. 204, 77–87 (1978)
Chen, G., Ensor, C. R., Russel, D., Bohner, B.: The pharmacology of 1-(1-phenylcyclohexyl)piperidine hydrochloride. J. Pharmacol. Exp. Ther. 127, 241–250 (1959)
Chen, G., Ensor, C. R., Bohner, B.: An investigation on sympothomimetic properties of phencyclidine by comparison with cocaine and desoxyephedrine. J. Pharmacol. Exp. Ther. 149, 71–78 (1965)
Dews, P. B.: Psychopharmacology. In: Experimental foundations of clinical psychology, A. J. Backrack, ed., pp. 423–441. New York: Basic Books 1962
Dews, P. B.: Behavioral tolerance. NIDA Res. Monogr. 18, 18–26 (1978)
Domino, E. F.: Neurobiology of phencyclidine (Sernyl), a drug with an unusual spectrum of pharmacological activity. Int. Rev. Neurobiol. 6, 303–347 (1964)
Domino, E. F.: Some aspects of the pharmacology of phencyclidine. In: The psychopharmacology of hallucinogens, R. C. Stillman, R. E. Willette, eds., pp. 105–117. New York: Pergamon 1978
Eastman, J. W., Cohen, S. N.: Hypertensive crisis and death associated with phencyclidine poisoning. J. Am. Med. Ass. 231, 1270–1271 (1975)
Fauman, B., Baker, L. W., Coppkson, P. Rosen, Segal, M. B.: Psychosis induced by phencyclidine. J. Am. Coll. Emer. Physicians 4, 223 (1975)
James, S. H., Schnoll, S. H.: Phencyclidine: Tissue distribution in the rat. Clin. Toxicol. 9, 573–582 (1976)
Kovacic, B., Domino, E. F.: Tolerance and limited cross-tolerance to the effects of N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) on food-rewarded bar pressing in the rat. J. Pharmacol. Exp. Ther. 197, 495–502 (1976)
Kovacic, B., Lu, L. J. Wang, Ruffing, D., Domino, E. F.: Interactions of partial LSD analogs with behavioral disrupting effects of LSD and DMT in the rat. Eur. J. Pharmacol. 47, 37–44 (1978)
Krasnegor, N. A., ed.: Behavioral tolerance: Research and treatment implications. NIDA Res. Monogr. 18, 1–151 (1978)
LeBlanc, A. E., Gibbins, R. J., Kalant, H.: Behavioral augmentation of tolerance to ethanol in the rat. Psychopharmacologia 30, 117–122 (1973)
Linden, C. B., Lovejoy, F. H., Jr., Costello, C. E.: Phencyclidine. J. Am. Med. Ass. 234, 513–516 (1975)
Luby, E. D., Gottlieb, J., Cohen, B., Rosenbaum, G., Domino, E. F.: Model psychoses and schizophrenia. Am. J. Psychiatry 119, 61–67 (1962)
McKearney, J. W., Barrett, J. E.: Schedule-controlled behavior and the effects of drugs. In: Contemporary research in behavioral pharmacology, D. E. Blackman, D. J. Sanger, eds., pp. 1–68. New York: Plenum 1978
Ruffing, D., Kovacic, B., Demetriou, S., Domino, E. F.: Naloxone enhancement of DMT- and LSD-25-induced suppression of food-rewarded bar pressing behavior in the rat. Psychopharmacology 62, 207–210 (1979)
Snedecor, G. W.: Statistical methods. Ames: Iowa State College Press 1956
Tong, T. G., Benowitz, N. L., Becker, C. E., Forni, P. J., Boerner, U.: Phencyclidine poisoning. J. Am. Med. Ass. 234, 512–513 (1975)
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Ruffing, D.M., Domino, E.F. First dose behavioral tolerance to phencyclidine on food-rewarded bar pressing behavior in the rat. Psychopharmacology 69, 1–4 (1980). https://doi.org/10.1007/BF00426513
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DOI: https://doi.org/10.1007/BF00426513