Psychopharmacology

, Volume 101, Issue 4, pp 519–524 | Cite as

Sensitization versus tolerance to the dopamine turnover-elevating effects of haloperidol: the effect of regular/intermittent dosing

  • John G. Csernansky
  • Elisabeth P. Bellows
  • Deborah E. Barnes
  • Leon Lombrozo
Original Investigations

Abstract

Recent clinical research suggests that particular patterns of changes in presynaptic dopamine (DA) turnover accompany the therapeutic response to neuroleptics. We sought to determine whether daily versus weekly dosing of haloperidol for 3 weeks produced distinct effects on DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) concentrations in multiple brain areas. Daily dosing favored the development of tolerance to the DA-turnover elevating effects of haloperidol in the striatum and nucleus accumbens. Weekly dosing favored the development of sensitization in the striatum, posterior olfactory tubercle, and ventral tegmental area. These results suggest that dosing schedules may determine, at least in part, the effects of chronic neuroleptic administration on presynaptic DA function.

Key words

Dopamine turnover Dihydroxyphenylacetic acid Homovanillic acid Sensitization Neuroleptic 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Antelman SM, Eichler AJ, Black CA, Kocan D (1980) Interchange-ability of stress and amphetamine in sensitization. Science 207:329–331Google Scholar
  2. Antelman SM, DeGiovanni LA, Kocan D, Perel JM, Chiodo LA (1983) Amitriptyline sensitization of a serotonin-mediated behavior depends on the passage of time and not repeated treatment. Life Sci 33:1727–1730Google Scholar
  3. Antelman SM, Kocan D, Edwards DJ, Knopf S, Perel JM, Stiller R (1986) Behavioral effects of a single neuroleptic treatment grow with the passage of time. Brain Res 385:58–67Google Scholar
  4. Asper H, Baggiolini M, Burki HR, Lauener H, Ruch W, Stille G (1973) Tolerance phenomena with neuroleptics catalepsy, apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol. Eur J Pharmacol 22:287–294Google Scholar
  5. Bacopoulos NG, Bustos G, Redmond DE, Jr, Roth RH (1982) Chronic treatment with haloperidol or fluphenazine decanoate: regional effects on dopamine and serotonin metabolism in primate brain. J Pharmacol Exp Ther 221:22–28Google Scholar
  6. Bannon MJ, Bunney EB, Zigun JR, Skirboll LR, Roth RH (1980) Presynaptic dopamine receptors: insensitivity to kainic acid and the development of supersensitivity following chronic haloperidol. Naunyn-Schmiedeberg's Arch Pharmacol 312:161–165Google Scholar
  7. Blanc G, Herve D, Simon H, Lisoprawski A, Glowinski J, Tassin JP (1980) Response to stress of mesocortico-frontal dopaminergic neurones in rats after long-term isolation. Nature 284:265–267Google Scholar
  8. Bowers MB Jr, Hoffman FJ Jr (1986) Homovanillic acid in caudate and pre-frontal cortex following acute and chronic neuroleptic administration. Psychopharmacology 88:63–65Google Scholar
  9. Bowers MB Jr, Rozitis A (1976) Brain homovanillic acid: regional changes over time with antipsychotic drugs. Eur J Pharmacol 39:109–115Google Scholar
  10. Bowers MB Jr, Swigar ME, Jatlow MD, Goicoechea N (1984) Plasma catecholamine metabolites and early response to haloperidol. J Clin Psychiatry 45:248–251Google Scholar
  11. Bunney BS (1988) Effects of acute and chronic neuroleptic treatment on the activity of midbrain dopamine neurons. Ann NY Acad Sci 537:77–85Google Scholar
  12. Carlson JH, Bergstrom DA, Weick BG, Walters JR (1987) Neurophysiological investigation of effects of D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons. Synapse 1:411–416Google Scholar
  13. Casey DE (1987) Tardive dyskinesia. In: Meltzer HY (ed) Psychopharmacology the third generation of progress. Raven Press, New York, pp 1411–1419Google Scholar
  14. Chang WH, Yeh EK, Hu WH, Tseng YT, Chung MC, Chang HF (1986) Acute and chronic effects of haloperidol on plasma and brain homovanillic acid in the rat. Biol Psychiatry 21:374–381Google Scholar
  15. Coyle S, Napier TC, Breese GR (1985) Ontogeny of tolerance to haloperidol: behavioral and biochemical measures. Dev Brain Res 23:27–38Google Scholar
  16. Davila R, Manero E, Zumarraga M, Andia I, Schweitzer JW, Friedhoff AJ (1988) Plasma homovanillic acid as a predictor of response to neuroleptics. Arch Gen Psychiatry 45:564–567Google Scholar
  17. Eilam D, Szechtman H (1989) Biphasic effect of D-2 agonist quinpirole on locomotion and movements. Eur J Pharmacol 161:151–157Google Scholar
  18. Finlay JM, Jakubovic A, Fu DS, Fibiger HC (1987) Tolerance to haloperidol-induced increases in dopamine metabolites: fact or artifact? Eur J Pharmacol 137:117–121Google Scholar
  19. Kashihara K, Sato M, Fujiwara Y, Harada T, Ogawa T, Otsuki S (1986) Effects of intermittent and continuous haloperidol administration on the dopaminergic system in the rat brain. Biol Psychiatry 21:650–656Google Scholar
  20. Koller W, Herbster G, Anderson D, Wack R, Gordon J (1987) Quinpirole hydrochloride, a potential anti-parkinsonism drug. Neuropharmacology 26:1031–1036Google Scholar
  21. Matsumoto T, Uchimura H, Hirano M, Kim JS, Yokoo H, Shimomura M, Nakahara T, Inoue K, Oomagari K (1983) Differential effects of acute and chronic administration of haloperidol on homovanillic acid levels in discrete dopaminergic areas of rat brain. Eur J Pharmacol 89:27–33Google Scholar
  22. Muller P, Seeman P (1978) Dopaminergic supersensitivity after neuroleptics: time-course and specificity. Psychopharmacology 60:1–11Google Scholar
  23. Nicolaou NM (1980) Acute and chronic effects of neuroleptics and acute effects of apomorphine and amphetamine on dopamine turnover in corpus striatum and substantia nigra of the rat brain. Eur J Pharmacol 64:123–132Google Scholar
  24. Nowak JZ, Arbilla S, Galzin AM, Langer SZ (1983) Changes in sensitivity of release modulating dopamine autoreceptors after chronic treatment with haloperidol. J Pharmacol Exp Ther 226:558–564Google Scholar
  25. Paxinos G, Watson C (1986) The rat brain in stereotactic coordinates, 2nd edn. Harcourt Brace Jovanovich, New YorkGoogle Scholar
  26. Pickar D, Labarca R, Doran AR, Wolkowitz OM, Roy A, Breier A, Linnoila M, Paul SM (1986) Longitudinal measurement of plasma homovanillic acid levels in schizophrenic patients. Arch Gen Psychiatry 43:669–676Google Scholar
  27. Post RM (1980) Minireview: Intermittent versus continuous stimulation: effect of time interval on the development of sensitization or tolerance. Life Sci 26:1275–1282Google Scholar
  28. Prosser ES, Pruthi R, Csernansky JG (1989) Differences in the time course of dopaminergic supersensitivity following chronic administration of haloperidol, molindone, or sulpiride. Psychopharmacology 99:109–116Google Scholar
  29. Puri SK, Lal H (1974) Tolerance to the behavioral and neurochemical effects of haloperidol and morphine in rats chronically treated with morphine or haloperidol. Naunyn-Schmiedeberg's Arch Pharmacol 282:155–170Google Scholar
  30. Saller CF, Salama AI (1985) Alterations in dopamine metabolism after chronic administration of haloperidol. Neuropharmacology 24:123–129Google Scholar
  31. Sayers AC, Burki HR, Ruch W, Asper H (1975) Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of clozapine, haloperidol, loxapine and chlorpromazine. Psychopharmacologia 41:97–104Google Scholar
  32. Scatton B (1977) Differential regional development of tolerance to increases in dopamine turnover upon repeated neuroleptic administration. Eur J Pharmacol 46:363–369Google Scholar
  33. Scatton B (1980) Effect of repeated treatment with neuroleptics on dopamine metabolism in cell bodies and terminals of dopaminergic systems in the rat brain. Adv Biochem Psychopharmacol 24:31–36Google Scholar
  34. Strong R (1988) Regionally selective manifestations of neostriatal aging. Ann NY Acad Sci 515:161–177Google Scholar
  35. Watanabe H (1984) Activation of dopamine synthesis in mesolimbic dopamine neurons by immobilization stress in the rat. Neuropharmacology 23:1335–1338Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • John G. Csernansky
    • 1
    • 2
  • Elisabeth P. Bellows
    • 2
  • Deborah E. Barnes
    • 1
  • Leon Lombrozo
    • 2
  1. 1.Department of Psychiatry and Behavioral SciencesStanford University School of MedicineStanfordUSA
  2. 2.Department of Veterans Affairs Medical Center (116A8)Laboratory of Clinical PsychopharmacologyPalo AltoUSA

Personalised recommendations