Abstract
The development of circling behavior to apomorphine, amphetamine and l-Dopa in mice with unilateral 6-hydroxydopamine lesions of the dopaminergic nerve terminals in the striatum has been studied, and the effect of a range of neuroleptic and sedative drugs on this circling behaviour has been investigated. Circling induced by all the stimulant drugs was inhibited in a dose-dependent manner by haloperidol, pimozide, chlorpromazine, metoclopramide and clozapine (in descending rank order of potency), but not by phenoxybenzamine, diazepam, promethazine and pentobarbitone sodium. This relatively simple animal model appears useful for screening neuroleptic drugs which may block striatal dopamine receptors, thereby predicting their potency to cause unwanted extrapyramidal effects but not their antipsychotic efficacy.
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Andén, N.-E., Dahlstrom, A., Fuxe, K., Larsson, K.: Functional role of the nigro-neostriatal dopamine neurons. Acta pharmacol. (Kbh.) 24, 263–274 (1966)
Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)
Andén, N.-E., Stock, G.: Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J. Pharm. Pharmacol. 25, 346–348 (1973)
Armitage, P.: Statistical methods in medical research, pp. 249–250. New York: Wiley 1971
Ayd, F. J., Jr.: Clozapine: A unique new neuroleptic. Intern. Drug Ther. Newsletter 9, 5–12 (1974)
Bobon, D. P., Janssen, P. A. J., Bobon, J.: Modern problems of pharmopsychiatry, The Neuroleptics, vol. 5. Basel: Karger 1970
Casteels-Van Daele, M., Jaeken, J., Van der Schueren, P., Zimmerman, A., Van den Bon, P.: Dystonic reactions in children caused by metoclopramide. Arch. Dis. Childh. 45, 130–133 (1970)
Chang, C. C.: A sensitive method for spectrophotofluorometric assay of catecholamines. Int. J. Neuropharmacol. 3, 643–649 (1964)
Christie, J. E., Crow, T. J.: Turning behavior as an index of the action of amphetamines and ephedrines on central dopamine-containing neurones. Brit. J. Pharmacol. 43, 658–667 (1971)
Costall, B., Naylor, R. J.: The role of telencephalic dopaminergic systems in the mediation of apomorphine-stereotyped behavior. Europ. J. Pharmacol. 24, 8–24 (1973)
Costall, B., Naylor, R. J.: Actions of dopaminergic agonists on motor function. In: Dopaminergic mechanisms, advances in neurology, Vol. 9, D. B. Calne, T. N. Chase, A. Barbeau, eds., pp. 285–297. New York: Raven Press 1975
Creese, I., Iversen, S. D.: The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacologia (Berl.) 39, 345–357 (1974)
Crow, T. J., Gillbe, C.: Dopamine antagonism and anitischizophrenic potency of neuroleptic drugs. Nature (New Biol.) 245, 27–28 (1973)
Dolphin, A., Jenner, P., Marsden, C. D., Pycock, C., Tarsy, D.: Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents. Psychopharmacologia (Berl.) 41, 133–138 (1975)
Falck, B., Hillarp, N. A., Thieme, G., Torp, A.: Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10, 348–354 (1962)
Fog, R.: On stereotypy and catalepsy: Studies on the effect of amphetamines and neuroleptics in rats. Acta neurol. scand. 48, Suppl. 50, 1–66 (1972)
Fuxe, K., Agnati, L. F., Corrodi, H., Everitt, B. J., Hökfelt, T., Löfström, A., Ungerstedt, U.: Action of dopamine receptor agonists in forebrain and hypothalamus: Rotational behavior, ovulation, and dopamine turnover. In: Dopaminergic mechanisms, advances in neurology, Vol. 9, D. B. Calne, T. N. Chase, and A. Barbeau, eds., pp. 223–242. New York: Raven Press 1975
Hackman, R., PentikÄinen, P. J., Neuvonen, P. J., Vapaatalo, H.: Inhibition of the apomorphine gnawing compulsion by amantadine. Experientia (Basel) 34, 1524–1525 (1973)
Lotti, V. J.: Action of varous centrally acting agents in mice with unilateral caudate brain lesions. Life Sci. 10, 781–789 (1971)
Laverty, R., Sharman, D. F.: The estimation of small quantities of 3,4-dihydroxyphenylalanine in tissues. Brit. J. Pharmacol. 24, 538–548 (1965)
Maickel, R. P., Cox, R. H., Saillant, J., Miller, F. P.: A method for the determination of serotonin and norepinephrine in discrete areas of rat brain. Int. J. Neuropharmacol. 7, 275–281 (1968)
Matthysse, S.: Antipsychotic drug actions: A clue to the neuropathology of schizophrenia? Fed. Proc. 32, 200–205 (1973)
Miller, R. J., Hiley, C. R.: Antimuscarinic properties of neuroleptics and drug-induced parkinsonism. Nature (Lond.) 248, 596–597 (1974)
Moore, K. E., Thornburg, J. E.: Drug-induced dopaminergic supersensitivity. In: Dopaminergic mechanisms, advances in neurology, Vol. 9, D. B. Calne, T. N. Chase, and A. Barbeau, eds., pp. 93–104. New York: Raven Press 1975
Rolinski, Z., Scheel-Krüger, J.: The effect of dopamine and noradrenaline antagonists on amphetamine induced locomotor activity in mice and rats. Acta pharmacol. (Kbh.) 33, 385–399 (1973)
Thierry, A. M., Stinus, L., Blanc, G., Glowinski, J.: Some evidence for the existence of dopaminergic neurons in the rat cortex. Brain Res. 50, 230–234 (1973)
Thornburg, J. E., Moore, K. E.: The relative importance of dopaminergic and noradrenergic neuronal systems for the stimulation of locomotor activity induced by amphetamine and other drugs. Neuropharmacology 12, 853–866 (1973)
Thornburg, J. E., Moore, K. E.: A comparison of effects of apomorphine and ET495 on locomotor activity and circling behavior in mice. Neuropharmacology 13, 189–197 (1974)
Ungerstedt, U.: Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behavior. Acta physiol. scand. 82, Suppl. 367, 49–68 (1971a)
Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand. 82, Suppl. 367, 69–93 (1971b)
von Voigtlander, P. F., Moore, K. E.: Turning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum: Effects of apomorphine, l-Dopa, amantadine amphetamine, and other psychomotor stimulants. Neuropharmacology 12, 451–462 (1973)
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Pycock, C., Tarsy, D. & Marsden, C.D. Inhibition of circling behavior by neuroleptic drugs in mice with unilateral 6-hydroxydopamine lesions of the striatum. Psychopharmacologia 45, 211–219 (1975). https://doi.org/10.1007/BF00429063
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DOI: https://doi.org/10.1007/BF00429063