Skip to main content
Log in

Haloperidol- and SCH23390-induced dopaminergic supersensitivities are not additive in the rat

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

The effect of chronic D-1 and/or D-2 dopamine receptor blockade on apomorphine-induced behaviors was studied in rats treated for 21 days with the selective D-1 antagonist SCH23390, the predominantly D-2 antagonist haloperidol, and the combination of the two drugs at the same daily doses (0.1 and 1 mg/kg respectively). Apomorphine (0.3 mg/kg) 4 days following the last injection of the drugs increased (49–70%) stereotypic behavior in all animals as compared to saline-treated controls. Although the SCH23390-induced increase was lower than haloperidol-induced supersensitivity, stereotypies after combined administration of both drugs did not differ significantly from either, suggesting that the effects of the two drugs are not additive. Underlying receptor changes and modified D-1/D-2 receptor interactions may account for the participation of both receptor subtypes to the development of neuroleptic-induced dopaminergic supersensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Baldessarini RJ, Tarsy D (1979) Relationship of the actions of neuroleptic drugs to the pathophysiology of tardive dyskinesia. Int Rev Neurobiol 21:1–45

    Google Scholar 

  • Barone P, Davis TA, Braun AR, Chase TN (1986) Dopaminergic mechanisms and motor function: characterization of D-1 and D-2 receptor interactions. Eur J Pharmacol 123:109–114

    Google Scholar 

  • Barone P, Tucci I, Parashos SA, Chase TN (1988) Supersensitivity to a D-1 agonist and subsensitivity to a D-2 agonist following chronic D-1 receptor blockade. Eur J Pharmacol 149:225–232

    Google Scholar 

  • Braun AR, Barone P, Chase TN (1986) Interaction D1 and D2 dopamine receptors in the expression of dopamine agonist induced behaviors. In: Breese GR, Creese I (eds) Neurobiology of central D1 dopamine receptors. Plenum Press Corporation, New York, pp 151–166

    Google Scholar 

  • Chipkin RE, McQuade RD, Iorio LC (1987) D-1 and D-2 binding site upregulation and apomorphine-induced stereotypy. Pharmacol Biochem Behav 28:477–482

    Google Scholar 

  • Christensen AV, Arnt J, Hyttel J, Larsen JJ, Svendsen O (1984) Pharmacological effects of a specific dopamine D-1 antagonist SCH23390 in comparison with neuroleptics. Life Sci 34:1529–1540

    Google Scholar 

  • Christensen AV, Arnt J, Sevendsen O (1985) Pharmacological differentiation of D-1 and D-2 antagonists after single and repeated administration. In: Casey D, Chase TN, Christensen AV, Gerlach J (eds) Dyskinesia—research and treatment. Springer, Berlin Heidelberg New York Tokyo, pp 182–190

    Google Scholar 

  • Costall B, Naylor RJ (1973) Neuroleptic and non-neuroleptic catalepsy. Arzneimittelforschung 23:674–683

    Google Scholar 

  • Creese I, Chen A (1985) Selective D-1 dopamine receptor increase following chronic treatment with SCH23390. Eur J Pharmacol 109:127–128

    Google Scholar 

  • Creese I, Sibley DR, Hamblin MN, Leff SE (1983) The classification of dopamine receptors: relationship to radioligand binding. Annu Rev Neurosci 6:43–71

    Google Scholar 

  • Ernst AM (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10:316–323

    Google Scholar 

  • Fleminger S, Rupniak NMJ, Hall MD, Jenner P, Marsden CD (1983) Changes in apomorphine-induced stereotypy as a result of subacute neuroleptic treatment correlates with increased D-2 receptors but not with increases in D-1 receptors. Biochem Pharmacol 32:2921–2927

    Google Scholar 

  • Fray PJ, Sahakian BJ, Robbins TW, Koob GF, Inversen SD (1980) An observational method for quantifying the behavioural effects of dopamine agonists: contrasting effects of d-amphetamine and apomorphine. Psychopharmacology 69:253–259

    Google Scholar 

  • Gianutsos G, Drawbaugh RB, Hynes MD, Lal H (1974) Behavioural evidence for dopaminergic supersensitivity after haloperidol. Life Sci 14:887–898

    Google Scholar 

  • Goetz CG, Carvey PM, Tanner CM, Klawans HL (1984) Neuroleptic-induced dopamine hyposensitivity. Life Sci 34:1475–1479

    Google Scholar 

  • Hess EJ, Albers LJ, Le H, Cresse I (1986) Effects of chronic SCH23390 treatment on the biochemical and behavioral properties of D-1 and D-2 dopamine receptors: potentiated behavioral responses to a D-2 dopamine agonist after selective D-1 dopamine receptor upregulation. J Pharmacol Exp Ther 238:846–854

    Google Scholar 

  • Hyttel J, Christensen AV, Arnt J (1983) Neuroleptic classification: Implications for tardive dyskinesia. Mod Probl Pharmacopsychiatry 21:49–64

    Google Scholar 

  • Jenner P, Marsden CD (1986) Interactions between D-1 and D-2 receptors resulting from chronic neuroleptic action. Clin Neuropharmacol [Suppl] 9:26–28

    Google Scholar 

  • Kilts CD, Dew KL, Ely TD, Mailman RB (1985) Quantification of R-(+)-7choloro-8-hydroxy-1-phenyl1,2,3,4,5,tetrahydro-1H-3-methyl-3-benzazepine in brain and blood by use of reversed-phase high performance liquid chromatography with electrochemical detection. J Chromatogr 342:452–457

    Google Scholar 

  • Mailman RB, Schulz DW, Lewis MH, Staples L, Rollma H, Dehaven DL (1984) SCH 23390: a selective D-1 dopamine antagonist with potent D-2 behavioral actions. Eur J Pharmacol 101:159–160

    Google Scholar 

  • Memo M, Pizzi M, Missale C, Carruba MO, Spano RF (1987) Modification of the function of the D-1 and D-2 dopamine receptors in striatum and nucleus accumbens of rats chronically treated with haloperidol. Neuropharmacology 26:477–480

    Google Scholar 

  • Molloy AC, Waddington JL (1984) Dopaminergic behavior stereo-specifically promoted by the D1 agonist R-SK & F38393 and selectively blocked by the D1 antagonist SCH23390. Psychopharmacology 82:409–410

    Google Scholar 

  • Parashos SA, Barone P, Tucci I, Chase TN (1987) Attenuation of D-1 antagonist-induced D-1 receptor upregulation by concomitant D-2 receptor blockade. Life Sci 41:2279–2284

    Google Scholar 

  • Porceddu ML, Ongini E, Biggio G (1985) 3H-SCH23390 binding sites increase after chronic blockade of D-1 dopamine receptors. Eur J Pharmacol 118:367–370

    Google Scholar 

  • Rastogi SK, Rastogi RB, Singhal RL, Lapierre YD (1983) Behavioral and biochemical alterations following haloperidol treatment and withdrawal: the animal model of tardive dyskinesia reexamined. Prog Neuropsychopharmacol. Biol Psychiatry 9:153–164

    Google Scholar 

  • Saller CF, Salama AI (1986) D-1 and D-2 dopamine receptor blockade: interactive effects in vitro and in vivo. J Pharmacol Exp Ther 236:714–720

    Google Scholar 

  • Schelkunov EL (1967) Adrenergic effects of chronic administration of neuroleptics. Nature 214:1210–1212

    Google Scholar 

  • Schulz DW, Staples L, Mailman RB (1985) SCH23390 causes persistent antidopaminergic effects in vivo: evidence for long-term occupation of receptors. Life Sci 36:1941–1948

    Google Scholar 

  • Walters JR, Bergstrom DA, Carlson JH, Chase TN, Braun AR (1987) D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects. Science 236:719–722

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parashos, S.A., Barone, P., Marin, C.A. et al. Haloperidol- and SCH23390-induced dopaminergic supersensitivities are not additive in the rat. Psychopharmacology 98, 189–192 (1989). https://doi.org/10.1007/BF00444690

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00444690

Key words

Navigation