, Volume 76, Issue 1, pp 52–56 | Cite as

Behavioral effects of chronic phencyclidine administration in rats

  • R. David Sturgeon
  • Richard G. Fessler
  • Scott F. London
  • Herbert Y. Meltzer
Original Investigations


The development of tolerance to phencyclidine (PCP) was examined in rats using behavioral rating scales with simultaneous measurements of locomotor activity, stereotyped behaviors, and ataxia. Significant tolerance to the stereotyped behaviors and ataxia induced by 5 or 10 mg/kg PCP was found on day 5 of chronic drug treatment. Because ataxia interferes with PCP-induced locomotor activity (Sturgeon et al. 1979), tolerance to PCP-induced ataxia produced an increase in locomotor activity on day 5. Tolerance to the ataxia, but not to the stereotyped behaviors induced by PCP, was more prominent after day 15 of PCP administration than after day 5. Administration of PCP for 15 days resulted in a significant decrease in locomotor activity for the 5 mg/kg group but not for the 10 mg/kg group. These results suggest that behavioral tolerance, rather than supersensitivity, develops after chronic PCP administration. The effects of PCP returned to baseline over a 14-day withdrawal period for rats treated with 5 mg/kg PCP for 15 days. Rats treated with 10 mg/kg PCP for 15 days still had not returned to baseline when tested 28 days after cessation of PCP treatment.

Key words

Phencyclidine Locomotor activity Stereotyped behaviors Ataxia Tolerance 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Balster RL, Chait LD (1976) The behavioral pharmacology of phencyclidine. Clin Toxicol 9:513–528Google Scholar
  2. Chait LD, Balster RL (1978) The effects of acute and chronic phencyclidine on schedule-controlled behavior in the squirrel monkey. J Pharmacol Exp Ther 204:77–87Google Scholar
  3. Eichler AJ, Antelman SM, Black CA (1980) Amphetamine stereotypy is not a homogeneous phenomenon: sniffing and licking show distinct profiles of sensitization and tolerance. Psychopharmacology 68:287–290Google Scholar
  4. Fauman MA, Fauman BJ (1978) The psychiatric aspects of chronic phencyclidine use: A study of chronic PCP users. In: Petersen RC, Stillman RC (eds) Phencyclidine (PCP) abuse: an appraisal. NIDA Res. Monograph 21, Rockville, MD, pp. 183–200Google Scholar
  5. Fauman MA, Fauman BJ (1980) Chronic phencyclidine (PCP) abuse: A psychiatric perspective—Part I: General aspects and violence. Psychopharmacol Bull 16:70–72Google Scholar
  6. Flint BA, Ho IK (1980) Tolerance development to phencyclidine by chronic administration. Prog Neuro-Psychopharmacol 4:223–239Google Scholar
  7. Hitzemann RJ, Tseng LF, Hitzemann BA, Sampath-Khanna S, Loh HH (1977) Effects of withdrawal from chronic amphetamine intoxication on exploratory and stereotyped behaviors in the rat. Psychopharmacology 54:295–302Google Scholar
  8. Ho IK, Flint BA, Onoda K, Berndt WO (1978) Development of crosstolerance to barbiturate by phencyclidine chronic administration. Pharmacologist 20:165Google Scholar
  9. Hsu LL, Smith RC, Rolsten C, Leelavathi DE (1980) Effects of acute and chronic phencyclidine on neurotransmitter enzymes in rat brain. Biochem Pharmacol 29:2524–2526Google Scholar
  10. Kilbey MM, Ellinwood EH (1977) Chronic administration of stimulant drugs: Response modification. In: Ellinwood EH, Kilbey MM (eds) Cocaine and other stimulants. Plenum, New York, pp 409–429Google Scholar
  11. Kloog Y, Rehavi M, Maayani S, Sokolovsky M (1977) Anticholinesterase and antiacetylcholine activity of l-phencyclohexylamine derivatives. Eur J Pharmacol 45:221–227Google Scholar
  12. Leonard BE, Tonge SR (1970) Some aspects of an hallucinogenic drug (phencyclidine) on neurohumoral substances. Life Sci 9:1141–1152Google Scholar
  13. Lerner MS, Burns RS (1978) Phencyclidine use among youth: History, epidemiology and acute and chronic intoxication. In: Petersen RC, Stillman RC (eds) Phencyclidine (PCP) abuse: An appraisal. NIDA Res. Monograph 21. Rockville, MD, pp 66–118Google Scholar
  14. Maayani S, Weinstein H, Ben-Zvi N, Cohen S, Sokolovsky M (1974) Psychotomimetics as anticholinergic agents — I. l-Cyclohexylpiperidine derivatives: anticholinesterase activity and antagonistic activity to acetylcholine. Biochem Pharmacol 23:1263–1281Google Scholar
  15. Magos L (1969) Persistence of the effect of amphetamine on stereotyped activity in rats. Eur J Pharmacol 6:200–201Google Scholar
  16. Meltzer HY, Sturgeon RD, Simonovic M, Fessler RG (1981) Phencyclidine as an indirect dopamine agonist. In: Domino EF (ed) PCP (Phencyclidine): Historical and current perspectives. Ann Arbor, MI. NPP Books, pp 207–242Google Scholar
  17. Misra AL, Pontani RB, Bartolomeo J (1979) Persistence of phencyclidine (PCP) and metabolites in brain and adipose tissue and implications for long-lasting behavioral effects. Res Commun Chem Pathol Pharmacol 24:431–445Google Scholar
  18. Murray TF (1978) The effects of phencyclidine on operant behavior in the rat: biphasic effect and tolerance development. Life Sci 22:195–202Google Scholar
  19. Pinchasi I, Maayani S, Sokolovsky M (1977) On the interaction of drugs with the cholinergic nervous system. III. Tolerance to phencyclidine derivatives: In vivo and in vitro studies. Biochem Pharmacol 26:1671–1679Google Scholar
  20. Pinchasi I, Maayani S, Sokolovsky M (1978a) On the interaction of drugs with the cholinergic nervous system. I. Tolerance to phencyclidine derivatives in mice: pharmacologic characterization. Psychopharmacology 56:27–36Google Scholar
  21. Pinchasi I, Maayani S, Egozi Y, Sokolovsky M (1978b) On the interaction of drugs with the cholinergic nervous system. II. Crosstolerance between phencyclidine derivatives and cholinergic drugs. Psychopharmacology 56:37–40Google Scholar
  22. Rebec GV, Segal DS (1980) Apparent tolerance to some aspects of amphetamine stereotypy with long-term treatment. Pharmacol Biochem Behav 13:793–797Google Scholar
  23. Schlemmer RF, Jackson JA, Preston KL, Bederka JP, Garver DL, Davis JM (1978) Phencyclidine-induced stereotyped behavior in monkeys: antagonism by pimozide. Eur J Pharmacol 52:379–384Google Scholar
  24. Segal DS, Mandell AL (1974) Long-term administration of d-amphetamine: progressive augmentation of motor activity and stereotypy. Pharmacol Biochem Behav 2:249–255Google Scholar
  25. Smith RC, Biggs CA, Leelavathi DE, Altshuler HL (1978) Behavioral effects of acute and chronic phencyclidine in the rat. Neurosci Abstracts 4:503Google Scholar
  26. 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 59:169–179Google Scholar
  27. Woolverton WL, Balster RL (1979) Tolerance to the behavioral effects of phencyclidine: the importance of behavioral and pharmacological variables. Psychopharmacology 64:19–24Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • R. David Sturgeon
    • 1
    • 2
  • Richard G. Fessler
    • 1
    • 2
  • Scott F. London
    • 2
  • Herbert Y. Meltzer
    • 1
    • 2
  1. 1.Department of PsychiatryUniversity of Chicago, Pritzker School of MedicineChicagoUSA
  2. 2.Laboratory of Biological PsychiatryIllinois State Psychiatric InstituteChicagoUSA

Personalised recommendations