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Enhanced response to repeated d-amphetamine challenge: Evidence for behavioral sensitization in humans

  • Stephen M. Strakowski
    Correspondence
    Address reprint requests to Dr. Strakowski, Department of Psychiatry, University of Cincinnati College of Medicine, 231 Bethesda Ave., P.O. Box 670559, Cincinnati, OH 45267-0559.
    Affiliations
    Division of Psychotic Disorders Research, Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Kenji W. Sax
    Affiliations
    Division of Psychotic Disorders Research, Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Mark J. Setters
    Affiliations
    Division of Psychotic Disorders Research, Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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  • Paul E. Keck Jr
    Affiliations
    Division of Psychotic Disorders Research, Biological Psychiatry Program, Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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      Behavioral sensitization is the process whereby intermittent stimulant exposure produces a time-dependent, enduring, and progressively more robust behavioral response. This process serves as an important model of neural plasticity and has also been proposed as a model for a variety of psychiatric syndromes; however, there are no published controlled studies of behavioral sensitization in human subjects. The authors report results from a double-blind, placebo-controlled study of repeated d-amphetamine challenges in a sample of normal human volunteers. Eleven consecutively recruited normal volunteers participated in this 4-day protocol. Each subject received two daily doses of d-amphetamine (0.25 mg/kg) separated by 48 hours that alternated with two daily doses of matched placebo. Symptoms (activity/energy level, mood, rate, and amount of speech) and eye-blink rates were measured hourly for 5 hours following drug administration. All four measures demonstrated significantly enhanced increases following the second amphetamine dose as compared to the first amphetamine dose and both placebo conditions. These findings suggest that behavioral sensitization is measurable in human subjects.

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      References

        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        3rd ed rev. American Psychiatric Association, Baltimore1987
        • Angrist B
        • Corwin J
        • Bartlik B
        • Cooper T
        Early pharmacokinetics and clinical effects of oral d-amphetamine in normal subjects.
        Biol Psychiatry. 1987; 22: 1357-1368
        • Antelman SM
        • Eichler AJ
        • Black CA
        • Kocan D
        Interchangeability of stress and amphetamine in sensitization.
        Science. 1980; 297: 329-331
        • Antelman SM
        • Caggiula AR
        • Knopf S
        • et al.
        Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stress/foreign nature of drugs.
        Psychopharmacology. 1992; 107: 331-336
        • Antelman SM
        • Kocan D
        • Edwards DJ
        • Knopf S
        Anticonvulsant and other effects of diazepam grow with time after a single treatment.
        Pharmacol Biochem Behav. 1989; 33: 31-39
        • Antelman SM
        • Caggiula AR
        • Kocan D
        • et al.
        One experience with ‘lower’ or ‘higher’ intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: Implications for understanding drug variability.
        Brain Res. 1991; 566: 276-283
        • Antelman SM
        • Chiodo LA
        Amphetamine as a stressor.
        in: Creese I Stimulants: Neurochemical, Behavioral, and Clinical Perspectives. Raven Press, Washington DC1983: 269-299
        • Bell DS
        The experimental reproduction of amphetamine psychosis.
        Arch Gen Psychiatry. 1973; 29: 35-40
        • Brady KT
        • Lydiard RB
        • Malcolm R
        • Ballenger JC
        Cocaine-induced psychosis.
        J Clin Psychiatry. 1991; 52: 509-512
        • Carlson GA
        • Goodwin FK
        The stages of mania: A longitudinal analysis of the manic episode.
        Arch Gen Psychiatry. 1973; 28: 221-228
        • Castaneda E
        • Becker JB
        • Robinson TE
        The long-term effects of repeated amphetamine treatment in vivo on amphetamine, KCL, and electrical stimulation evoked striatal dopamine release in vivo.
        Life Sci. 1988; 42: 2447-2456
        • Connell PH
        Amphetamine Psychosis.
        in: Maudsley Monograph No. 5. Chapman & Hall Ltd, New York1958
        • Deutsch SI
        • Mastropaolo J
        • Schwartz BL
        • et al.
        A “glutamatergic hypothesis” of schizophrenia.
        Clin Neuropharmacol. 1989; 12: 1-13
        • Fibiger HC
        The dopamine hypothesis of schizophrenia and mood disorders.
        in: Willner P. Scheel-Kruger J. The mesuliactic dopamine system: from motivation to action. John Wiley & Sons, London1991
        • Goldberg TE
        • Begelow LB
        • Weinberger DR
        • et al.
        Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia.
        Am J Psychiatry. 1991; 148: 78-84
        • Goodwin FK
        • Jamison JR
        Manic-Depressive Illness.
        Oxford University Press, Chichester, England1990
        • Griffith JD
        • Cavanaugh J
        • Held J
        • Oates JA
        Dextroamphetamine: Evaluation of psychomimetic properties in man.
        Arch Gen Psychiatry. 1972; 26: 97-100
        • Jacobs D
        • Silverstone T
        Dextroamphetamine-induced arousal in human subjects as a model for mania.
        Psychol Med. 1986; 16: 323-329
        • Kalivas PW
        • Duffy P
        Effects of daily cocaine and morphine treatment on somatodendritic and terminal field dopamine release.
        J Neurochem. 1988; 50: 1498-1504
        • Karson CN
        Spontaneous eye-blink rates and dopaminergic systems.
        Brain. 1983; 106: 643-653
        • Klawans HL
        • Margolin DI
        Amphetamine-induced dopaminergic hypersensitivity in guinea pigs.
        Arch Gen Psychiatry. 1975; 32: 725-732
        • Klug JM
        • Norman AB
        Long-term sensitization of apomorphine-induced rotation behavior in rats with dopamine deafferentation or excitotoxin lesions of the striatum.
        Pharmacol Biochem Behav. 1993; 46: 397-403
        • Kokkinidis L
        Effects of chronic intermittent and continuous amphetamine administration on acoustic startle.
        Pharmacol Biochem Behav. 1984; 20: 367-372
        • Kuczenski R
        • Segal D
        Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis.
        J Neurosci. 1989; 9: 2051-2065
        • McNair DM
        • Lorr M
        • Droppleman LF
        Manual for the Profile of Mood States.
        EITS, New York1971
        • Overall JE
        • Gorham DR
        The Brief Psychiatric Rating Scale.
        Psychol Rep. 1962; 10: 799-812
        • Peris J
        • Zahniser NR
        One injection of cocaine produces a long-lasting increase in [3H]-dopamine release.
        Pharmacol Biochem Behav. 1987; 27: 533-535
        • Post RM
        Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.
        Am J Psychiatry. 1992; 149: 999-1010
        • Rebec GV
        • Segal DS
        Enhanced responsiveness to intraventricular infusion of amphetamine following its repeated systemic administration.
        Psychopharmacology. 1979; 13: 263-286
        • Reynolds GP
        Beyond the dopamine hypothesis: The neurochemical pathology of schizophrenia.
        Br J Psychiatry. 1989; 155: 305-326
        • Robinson TE
        Behavioral sensitization: Characterization of enduring changes in rotational behavior produced by intermittent injections of amphetamine in male and female rats.
        Psychopharmacology. 1984; 84: 466-475
        • Robinson TE
        • Becker JB
        Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis.
        Brain Res Rev. 1986; 11: 157-198
        • Robinson TE
        Stimulant drugs and stress: Factors influencing individual differences in the susceptibility to sensitization.
        in: Kalivas PW Barnes CD Sensitization in the Nervous System. Telford Press, San Diego, CA1988: 145-174
        • Satel SL
        • Southwick SM
        • Gawin FH
        Clinical features of cocaine-induced paranoia.
        Am J Psychiatry. 1991; 148: 495-498
        • Sato M
        • Chen CC
        • Akiyama K
        • Otsuki S
        Acute exacerbation of paranoid psychotic state after long-term abstinence in patients with previous methamphetamine psychosis.
        Biol Psychiatry. 1983; 18: 429-441
        • Schenk S
        • Valadez A
        • McNamara C
        • et al.
        Development and expression of sensitization to cocaine's reinforcing properties: Role of NMDA receptors.
        Psychopharmacol. 1993; 111: 332-338
        • Siegal S
        Learning and psychopharmacology.
        in: Jarvik ME Psychopharmacology in the Practice of Medicine. Appleton-Century-Crofts, Caldwell, NJ1977
        • Segal DS
        • Mandell AJ
        Long-term administration of amphetamine: Progressive augmentation of motor activity and stereotypy.
        Pharmacol Biochem Behav. 1974; 2: 249-255
        • Segal DS
        • Schuckit MA
        Animal models of stimulantinduced psychosis.
        in: Creese I Stimulants: Neurochemical, Behavioral, and Clinical Perspectives. Raven Press, New York1983
        • Segal DS
        • Geyer MA
        • Schuckit MA
        Stimulant-induced psychosis: An evaluation of animal models.
        in: Youdim MBH Lovenberg W Sharman DF Lagnado JR Essays in Neurochemistry and Neuropharmacology. Vol 5. John Wiley & Sons Ltd., New York, NY1981
        • Shtasel DL
        • Gur RE
        • Mozley PD
        • et al.
        Volunteers for biomedical research: Recruitment and screening of normal controls.
        Arch Gen Psychiatry. 1991; 48: 1022-1025
        • Spitzer RL
        • Williams JBW
        • Gibbon M
        • First MG
        Structured Clinical Interview for DSM-III-R—Patient Version (SCID-P).
        New York State Psychiatric Institute, Biometric Research, London1990
        • Stevens J
        Intermediate Statistics: A Modern Approach.
        Lawrence Erlbaum Associates, New York1990
        • Szechtman H
        • Cleghorn JM
        • Brown GM
        • et al.
        Sensitization and tolerance to apomorphine in men: Yawning, growth hormone, nausea, and hyperthermia.
        Psychiatry Res. 1988; 23: 245-255
        • Welkowitz J
        • Ewen RB
        • Cohen J
        Introductory Statistics for the Behavioral Sciences.
        Academic Press, Hillsdale, NJ1976
        • Wolf M
        • Jeziorski M
        Coadministration of MK-801 with amphetamine, cocaine or morphine prevents rather than transiently masks the development of behavioral sensitization.
        Brain Res. 1993; 613: 291-294
        • Yehuda R
        • Antelman SM
        Criteria for rationally evaluating animal models of posttraumatic stress disorder.
        Biol Psychiatry. 1993; 33: 479-486
        • Young RC
        • Biggs JT
        • Ziegler VE
        • Meyer DA
        A rating scale for mania: Reliability, validity and sensitivity.
        Br J Psychiatry. 1978; 133: 429-435