Abstract
The cataleptic behavior induced by the dopamine D1 antagonist SCH 23390 (SCH) has proven to be a useful assay for investigating the sensitivity of D1-like dopamine receptor-mediated effects during chronic drug administration. A fundamental flaw in most of these studies may be the involvement of the “repeated measures effect,” a behavioral phenomenon well demonstrated for neuroleptic-induced catalepsy but not yet investigated for dopamine D1 antagonists. In this study, mice exposed for various sessions to the bar test presented a strong sensitization to the cataleptic behavior induced by repeated SCH treatment. Conversely, single tested animals exhibited a trend toward decreased catalepsy after repeated SCH treatment, which was in line with the development of a D1-like dopamine receptor supersensitivity suggested by an increase in SKF 38393-induced grooming behavior. Surprisingly, a challenge intraperitoneal saline injection increased the cataleptic behavior of single tested mice after long-term SCH treatment. This “injection-conditioned ” was also observed after repeated treatment with the dopamine D2 antagonists, haloperidol and metoclopramide. While these findings seem to explain some important contradictory data in the literature, they provide a new and simple animal model of the placebo effect.
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References
Amir S, Brown ZW, Amit Z, Ornstein K . (1981): Body pinch induces long lasting cataleptic like immobility in mice: Behavioral characterization and the effect of naloxone. Life Sci 28 (10): 1189–1194
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 (1): 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 (5): 287–294
Axelrod J, Reisine TD . (1984): Stress hormones: Their interaction and regulation. Science 224 (4648): 452–459
Barnes DE, Robinson B, Csernansky JG, Bellows EP . (1990): Sensitization versus tolerance to haloperidol-induced catalepsy: Multiple determinants. Pharmacol Biochem Behav 36 (4): 883–887
Brown J, Handley SL . (1980): The development of catalepsy in drug-free mice on repeated testing. Neuropharmacology 19 (7): 675–678
Campbell A, Baldessarini RJ . (1981): Tolerance to behavioral effects of haloperidol. Life Sci 29 (13): 1341–1346
Carey RJ . (1992): Pavlovian conditioning of L-dopa induced movement. Psychopharmacology 107(2–3):203–210
Christensen AV, Arnt J, Hyttel J, Larsen JJ, Svendsen O . (1984): Pharmacological effects of a specific dopamine D1 antagonist SCH 23390 in comparison with neuroleptics. Life Sci 34 (16): 1529–1540
Creese I, Chen A . (1985): Selective D1 dopamine receptor increase following chronic treatment with SCH 23390. Eur J Pharmacol 109 (1): 127–128
Di Chiara G . (1995): The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 38 (2): 95–137
Dijk S, Krugers HJ, Korf J . (1991): The effect of teophylline and immobilization stress on haloperidol-induced catalepsy and on metabolism in the striatum and hippocampus, studied with lactograph. Neuropharmacology 30 (5): 469–473
Ezrin-Waters C, Seeman P . (1977): Tolerance of haloperidol catalepsy. Eur J Pharmacol 41 (3): 321–327
Ferré S, Guix T, Prat G, Jane F, Casas M . (1990): Is experimental catalepsy properly measured? Pharmacol Biochem Behav 35 (4): 753–757
Frussa-Filho R, Otoboni JR, Uema FT, Palermo-Neto J . (1992): Effects of age and isolation on the evolution of catalepsy during chronic haloperidol treatment. Braz J Med.Biol Res 25 (9): 925–928
Frussa-Filho R, Palermo-Neto J . (1988): Effects of single and long-term metoclopramide administration on open-field and stereotyped behaviour of rats. Eur J Pharmacol 149 (3): 323–329
Frussa-Filho R, Palermo-Neto J . (1990): Effects of single and long-term administration of sulpiride on open-field and stereotyped behaviour of rats. Braz J Med Biol Res 23 (5): 463–472
György L, Pfeifer KA, Hajtman B . (1969): Modification of certain central nervous effects of haloperidol during long-term treatment in the mouse and rat. Psychopharmacologia (Berl) 16 (3): 223–233
Hansen TE, Hoffman WF . (1997): Drug-induced Parkinsonism. In: Yassa R, Nair NPV, Jeste DV (eds). Neuroleptic-Induced Movement Disorders. New York: Cambridge University Press, pp 341–380
Hess EJ, Albers LJ, Le H, Creese I . (1986): Effects of chronic SCH 23390 treatment on the biochemical and behavioral properties of D1 and D2 dopamine receptors: potentiated behavioral responses to a D2 dopamine agonist after selective D1 dopamine receptor up-regulation. J Pharmacol Exp Ther 238 (3): 846–854
Hess EJ, Norman AB, Creese I . (1988): Chronic treatment with dopamine receptor antagonists: behavioral and pharmacologic effects on D1 and D2 dopamine receptors. J Neurosci 8 (7): 2361–2370
Hillegaart V, Ahlenius S, Magnusson O, Fowler CJ . (1987): Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy and a conditioned avoidance response. Pharmacol Biochem Behav 27: 159–164
Hiroi N, White NM . (1989): Conditioned stereotypy: behavioral specification of the UCS and pharmacological investigation of the neural change. Pharmacol Biochem Behav 32 (1): 249–258
Hoffman DC, Beninger RJ . (1988): Conditional tolerance to haloperidol-induced catalepsy: Striatal dopamine receptor supersensitivity is a possible explanation. Psychopharmacology (Berl) 95 (1): 142–145
Hyttel J . (1983): SCH 23390—the first selective dopamine D1 antagonist. Eur J Pharmacol 91 (1): 153–154
Ikemoto S, Glazier BS, Murphy JM, McBride WJ . (1997): Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward. J Neurosci 17 (21): 8580–8587
Iwata S, Izumi K, Shimizu T, Fukuda T . (1989): Effects of repeated testing on the incidence of haloperidol-induced catalepsy in mice. Pharmacol Biochem Behav 33 (3): 705–707
Lipska BK, Jaskiw GE, Braun AR, Weinberger DR . (1995): Prefrontal cortical and hippocampal modulation of haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors in the rat. Biol Psychiatry 38: 255–262
Kinon BJ, Kane JM . (1989): Difference in catalepsy response in inbred rats during chronic haloperidol treatment is not predictive of the intensity of behavioral hypersensitivity which subsequently develops. Psychopharmacology (Berl) 98 (4): 465–471
Klemm WR . (1993): The catalepsy of blocked dopaminergic receptors. Psychopharmacology (Berl) 111 (2): 251–253
Lappalainen J, Hietala J, Syvälahti E . (1989): Differential tolerance to cataleptic effects of SCH 23390 and haloperidol after repeated administration. Psychopharmacology (Berl) 98 (4): 472–475
Lynch JJ, Stein EA, Fertziger AP . (1976): An analysis of 70 years of morphine classical conditioning: Implications for clinical treatment of narcotic addiction. J Nerv Mental Disease 163 (1): 47–58
Miller R, Wickens JR, Beninger RJ . (1990): Dopamine D1 and D2 receptors in relation to reward and performance: A case for the D1 receptor as a primary site of therapeutic action of neuroleptic drugs. Progr Neurobiol 34 (2): 143–183
Mizuki Y, Ushijima I, Yamada M . (1996): Effects of chronic methamphetamine on SCH 23390- or haloperidol- induced catalepsy, and effects of coadministration of SCH 23390 or haloperidol in mice. Pharmacol Biochem Behav 53 (2): 437–440
Moller Nielsen I, Fjalland B, Pedersen V, Nymark M . (1974): Pharmacology of neuroleptics upon repeated administration. Psychopharmacologia (Berl) 34 (2): 95–104
Molloy AG, Waddington JL . (1984): Dopaminergic behavior stereospecifically promoted by the D1 agonist R-SKF 38393 and selectively blocked by the D1 antagonist SCH 23390. Psychopharmacology 82 (4): 409–410
Parashos SA, Marin C, Barone P, Kapitzoglou-Logothetis V, Chase TN . (1990): Effect of chronic D1 and/or D2 dopamine antagonist treatment on SKF 38393-induced non-stereotyped grooming. Psychopharmacology 102 (3): 411–413
Pavlov IP . (1927): Conditioned Reflexes. London, Oxford University Press
Pickens RW, Crowder WF . (1967): Effects of CS-US interval on conditioning of drug response, with assessment of speed of conditioning. Psychopharmacologia 11 (1): 88–94
Rocha JB, Santos JE, Rocha LK, Kleinpaul ER . (1997): Undernutrition during suckling changes the sensitivity to haloperidol and chlorpromazine in two behavioural measures in weaning rats. Pharmacol Toxicol 81 (3): 114–123
Sanberg PR . (1980): Haloperidol-induced catalepsy is mediated by postsynaptic dopamine receptors. Nature 284 (5755): 472–473
Sanberg PR, Bunsey MD, Giordano M, Norman AB . (1988): The catalepsy test: its ups and downs. Behav Neurosci 102: 748–759
Schiff SR, Bridger WH, Sharless NS, King JJ . (1980): Conditioning using drugs affecting dopaminergic systems as unconditioned stimuli: Behavioral and biochemical evidence. Psychopharmacol Bull 16: 24–27
Schiff SR . (1982): Conditioned dopaminergic activity. Biol Psychiatry 17 (2): 135–155
Seeman P . (1980): Brain dopamine receptors. Pharmacol Rev 32: 229–313
St Jean A, Donald MW, Ban TA . (1964a): Uses and abuses of antiparkinsonian medication. Am J Psychiatry 120: 801–803
St Jean A, Donald M, Ban TA . (1964b): Interchangeability of Antiparkinsonian medication. Am J Psychiatry 120: 1189–1190
Stanley ME, Glick SD . (1976): Interaction of drug effects with testing procedures in the measurement of catalepsy. Neuropharmacology 15 (7): 393–394
Suchman AL, Ader R . (1992): Classic conditioning and placebo effects in crossover studies. Clin Pharmacol Ther 52 (4): 372–377
Tilson HA, Rech RH . (1973): Conditioned drug effects and absence of tolerance to d-amphetamine induced motor activity. Pharmacol Biochem Behav 1: 149–153
Undie AS, Friedman E . (1988): Differences in the cataleptogenic actions of SCH 23390 and selected classical neuroleptics. Psychopharmacology 96: 311–316
Ushijima I, Mizuki Y, Yamada M . (1995): Development of tolerance and reverse tolerance to haloperidol- and SCH 23390-induced cataleptic effects during withdrawal periods after long-term treatment. Pharmacol Bioch Behav 50 (2): 259–264
Vital MABF, Frussa-Filho R, Palermo-Neto J . (1995): Effects of monosialoganglioside on dopaminergic supersensitivity. Life Sci 56 (26): 2299–2307
Wise RA, Bozarth MA . (1987): A psychomotor stimulant theory of addiction. Psychol Reviews 94: 469–492
Wise RA, Rompre P-P . (1989): Brain dopamine and reward. Annu Rev Psychol 40: 191–225
Acknowledgements
This research was supported by a fellowship from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP—Proc. 97/12915–9 and Proc. 99/00526–3) and from Conselho Nacional de Desenvolvimento Cientıacute;fico e Tecnológico (CNPq—Proc. 522975/95–0).
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Chinen, C., Frussa-Filho, R. Conditioning to Injection Procedures and Repeated Testing Increase SCH 23390-Induced Catalepsy in Mice. Neuropsychopharmacol 21, 670–678 (1999). https://doi.org/10.1016/S0893-133X(99)00061-5
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DOI: https://doi.org/10.1016/S0893-133X(99)00061-5
