Research Article| Volume 22, ISSUE 3, P269-277, March 1987

Conditioning and the delayed onset of a haloperidol-induced behavioral effect

  • Robert J. Carey
    Address reprint requests to Dr. Robert J. Carey, Research and Development Service, VA Medical Center 800 Irving Avenue Syracuse, NY 13210.
    From SUNY-Upstate and VA Medical Centers, Syracuse, NYUSA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      In a series of experiments, rats were given daily injections of 0.3 mg/kg haloperidol or vehicle 1 hr prior to behavioral testing. In these experiments, when rats were placed in an illuminated compartment and given the opportunity to enter a darkened compartment, haloperidol- and vehicle-treated rats initially entered the dark compartment with similar latencies. With repeated treatments, however, the haloperidol group gradually took increasingly longer times to enter the dark compartment. Furthermore, when the drug treatments of the groups were reversed, behavioral performance was dissociated from the drug state of the animal. Vehicle rats switched to haloperidol entered the dark compartment much more rapidly than haloperidol rats switched to vehicle. As additional control procedures, rats were given haloperidol 1 hr posttrial or were given haloperidol and only placed in the dark compartment. These haloperidol treatments did not differ from vehicle treatments. The gradual development of long latencies to initiate behavior and the persistence of this behavior during withdrawal from the haloperidol are consistent with the establishment of a conditioned drug response. This observation suggests that conditioning may contribute to the delayed onset of response in the clinical use of neuroleptic drugs.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Asper H
        • Baggiolini M
        • Burki H
        • Lauener H
        • Ruch W
        • Stille G
        Tolerance phenomena with neuroleptics: Catalepsy, apomorphine stereotypies and straital dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol.
        Eur J Pharmacol. 1973; 22: 287-294
        • Barr G.A.
        • Sharpless N.S.
        • Cooper S
        • Schiff S.R.
        • Paredes W
        • Bridger W.H.
        Classical conditioning, decay and extinction of cocaine-induced hyperactivity and stereotypy.
        Life Sci. 1983; 33: 1341-1351
        • Biazzi A
        • Fregnan G.B.
        Behavioral, anti-dopaminergic and prohypnotic effects of neuroleptics during and after prolonged treatment.
        Adv Biochem Psychopharmacol. 1980; 24: 351-357
        • Bunney B.S.
        Antipsychotic drug effects on the electrical activity of dopaminergic neurons.
        TINS. 1984; (June): 212-215
        • Campbell A
        • Baldesarini R.J.
        Tolerance to behavioral effects of haloperidol.
        Life Sci. 1981; 29: 1341-1346
        • Carlsson A
        Antipsychotic drugs, neurotransmitters and schizophrenia.
        Am J Psychiatry. 1978; 135: 164-172
        • Erzin-Waters C
        • Seeman P
        Tolerance to haloperidol catalepsy.
        Eur J Pharmacol. 1977; 41: 321-327
        • Gilman A.G.
        • Goodman L.S.
        • Gilman A
        The Pharmacological Basis of Therapeutics.
        MacMillan, New York1980
        • Hayashi T
        • Ohashi K
        • Takokoro S
        Conditioned drug effects to d-amphetamine- and morphine-induced motor acceleration in mice: Experimental approach for placebo effect.
        Jpn J Pharmacol. 1980; 30: 93-100
        • Julou L
        • Scatton B
        • Glowinski J
        Acute and chronic treatment with neuroleptics: Similarities and differences in their action on nigrostriatal, mesolimbic and mesocortical dopaminergic neurons.
        in: Costa E Gessa G.L. Advances in Biochemical Pharmacology. Raven Press, New York1977: 617-624
        • Klein D.E.
        • Davis J.M.
        Diagnosis and Treatment of Psychiatric Disorders.
        Williams & Wilkins, Baltimore1969
        • Kokkinidis L
        • Zacharko R.M.
        Enhanced self-stimulation responding from the substantia nigra after chronic amphetamine treatment: A role for conditioning factors.
        Pharmacol Biochem Behav. 1980; 12: 543-547
        • Lloyd K.G.
        • Shibuya M
        • Davidson L
        • Hornykiewicz O
        Chronic neuroleptic therapy: Tolerance and GABA systems.
        Adv Biochem Psychopharmacol. 1977; 16: 409-415
        • Lynch M.R.
        • DeVeaugh-Geiss J
        • Kuhn G
        • Carey R.J.
        Acute haloperidol administration facilitates habituation processes.
        World Congr Biol Psychiatry Abstr. 1985; 4: 102
        • Mayer G.S.
        • Shoup R.E.
        Simultaneous multiple electrode liquid chromatographyelectrochemical assay for catecholamines, indoleamines and metabolites in brain tissue.
        J Chromatogr. 1983; 255: 533-544
        • Poulos C.X.
        • Hinson R
        Pavlovian conditional tolerance to haloperidol catalepsy: Evidence of dynamic adaptation in the dopaminergic system.
        Science. 1982; 218: 491-492
        • Scatton B
        Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration.
        Eur J Pharmacol. 1977; 46: 363-369
        • Schiff S.R.
        Conditioned dopaminergic activity.
        Biol Psychiatry. 1982; 17: 135-154
        • Thompson T
        • Schuster C.R.
        Behavioral Pharmacology.
        in: Prentice Hall, Englewood Cliffs, NJ1968: 160-162
        • Tilson H.A.
        • Rech R.H.
        Conditioned drug effects and absence of tolerance to d-amphetamine induced motor activity.
        Pharmacol Biochem Behav. 1973; 1: 149-153
        • Tyrer P.J.
        Drugs in Psychiatric Practice.
        Butterworths, London1982
        • Usdin E
        • Edkert H
        • Forrest I.S.
        Phenothiazines and Structurally Related Drugs: Basic and Clinical Studies.
        Elsevier North Holland, New York1980
        • Wise R.A.
        Neuroleptics and operant behavior: The anhedonia hypothesis.
        Behav Brain Sci. 1982; 5: 39-53