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.
Similar content being viewed by others
References
Antelman SM, Eichler AJ, Black CA, Kocan D (1980) Interchange-ability of stress and amphetamine in sensitization. Science 207:329–331
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 33:1727–1730
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 385:58–67
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 22:287–294
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 221:22–28
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 312:161–165
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 284:265–267
Bowers MB Jr, Hoffman FJ Jr (1986) Homovanillic acid in caudate and pre-frontal cortex following acute and chronic neuroleptic administration. Psychopharmacology 88:63–65
Bowers MB Jr, Rozitis A (1976) Brain homovanillic acid: regional changes over time with antipsychotic drugs. Eur J Pharmacol 39:109–115
Bowers MB Jr, Swigar ME, Jatlow MD, Goicoechea N (1984) Plasma catecholamine metabolites and early response to haloperidol. J Clin Psychiatry 45:248–251
Bunney BS (1988) Effects of acute and chronic neuroleptic treatment on the activity of midbrain dopamine neurons. Ann NY Acad Sci 537:77–85
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 1:411–416
Casey DE (1987) Tardive dyskinesia. In: Meltzer HY (ed) Psychopharmacology the third generation of progress. Raven Press, New York, pp 1411–1419
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 21:374–381
Coyle S, Napier TC, Breese GR (1985) Ontogeny of tolerance to haloperidol: behavioral and biochemical measures. Dev Brain Res 23:27–38
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 45:564–567
Eilam D, Szechtman H (1989) Biphasic effect of D-2 agonist quinpirole on locomotion and movements. Eur J Pharmacol 161:151–157
Finlay JM, Jakubovic A, Fu DS, Fibiger HC (1987) Tolerance to haloperidol-induced increases in dopamine metabolites: fact or artifact? Eur J Pharmacol 137:117–121
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 21:650–656
Koller W, Herbster G, Anderson D, Wack R, Gordon J (1987) Quinpirole hydrochloride, a potential anti-parkinsonism drug. Neuropharmacology 26:1031–1036
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 89:27–33
Muller P, Seeman P (1978) Dopaminergic supersensitivity after neuroleptics: time-course and specificity. Psychopharmacology 60:1–11
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 64:123–132
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 226:558–564
Paxinos G, Watson C (1986) The rat brain in stereotactic coordinates, 2nd edn. Harcourt Brace Jovanovich, New York
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 43:669–676
Post RM (1980) Minireview: Intermittent versus continuous stimulation: effect of time interval on the development of sensitization or tolerance. Life Sci 26:1275–1282
Prosser ES, Pruthi R, Csernansky JG (1989) Differences in the time course of dopaminergic supersensitivity following chronic administration of haloperidol, molindone, or sulpiride. Psychopharmacology 99:109–116
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 282:155–170
Saller CF, Salama AI (1985) Alterations in dopamine metabolism after chronic administration of haloperidol. Neuropharmacology 24:123–129
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 41:97–104
Scatton B (1977) Differential regional development of tolerance to increases in dopamine turnover upon repeated neuroleptic administration. Eur J Pharmacol 46:363–369
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 24:31–36
Strong R (1988) Regionally selective manifestations of neostriatal aging. Ann NY Acad Sci 515:161–177
Watanabe H (1984) Activation of dopamine synthesis in mesolimbic dopamine neurons by immobilization stress in the rat. Neuropharmacology 23:1335–1338
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Csernansky, J.G., Bellows, E.P., Barnes, D.E. et al. Sensitization versus tolerance to the dopamine turnover-elevating effects of haloperidol: the effect of regular/intermittent dosing. Psychopharmacology 101, 519–524 (1990). https://doi.org/10.1007/BF02244231
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244231