Abstract
The effect of the administration of l-Dopa, 10 or 100 mg/kg i.p., on the α-methyltyrosine methylester HCl (α-MT; 250+50 mg/kg i. p.) or tetrabenazine (TBZ; 2 mg/kg i.p.)-induced suppression of a successive discrimination-conditioned avoidance task has been studied. It was found that administration of the high l-Dopa dose resulted in a reversal of the α-MT- or TBZ-induced suppression of the avoidance behaviour, although the discrimination was lost. Restoration of the avoidance behaviour and the correct discrimination was obtained with the low l-Dopa dose after α-MT but not after TBZ. The difference in the behavioural response to l-Dopa after α-MT as compared to the response obtained after TBZ is discussed in terms of the availability of the catecholamines formed from l-Dopa for release by the nerve impulses. Biochemical determinations of brain noradrenaline and dopamine were made in parallel. Further, a simple and reliable method for the aquisition of a successive discrimination in the rat is described.
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Ahlenius, S.: Effects of l-Dopa on conditioned avoidance responding after behavioural suppression by α-methyltyrosine or reserpine in mice. Neuropharmacology (In press) 1974
Ahlenius, S., Andén, N.-E., Engel, J.: Importance of catecholamine release by nerve impulses for free operant behavior. Physiol. Behav. 7, 931–934 (1971)
Ahlenius, S., Andén, N.-E., Engel, J.: Restoration of locomotor activity in mice by low l-Dopa doses after suppression by α-methyltyrosine but not by reserpine. Brain Res. 62, 189–199 (1973)
Ahlenius, S., Engel, J.: Behavioural and biochemical effects of l-Dopa after inhibition of dopamine-Β-hydroxylase in reserpine pretreated rats. Naunyn-Schmiedebergs Arch. Phamak. 270, 349–360 (1971)
Ahlenius, S., Engel, J.: Antagonism by dl-thero-Dops of the suppression of a conditioned avoidance response induced by a dopamine-Β-hydroxylase inhibitor. J. Neural Transmission 34, 267–277 (1973)
Almgren, O., Lundborg, P.: Correlation of the recovery of the granular uptake-storage mechanism and the nerve impulse induced release of (3H)noradrenaline after reserpine. J. Pharm. Pharmacol. 23, 671–677 (1971)
Andén, N.-E.: Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anti-acetylcholine drugs. J. Pharm. Pharmacol. 24, 905–906 (1972)
Andén, N.-E., Bédard, P.: Influences of cholinergic mechanisms on the function and turnover of brain dopamine. J. Pharm. Pharmacol. 23, 460–462 (1971)
Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Atack, C. V.: The determination of dopamine by a modification of the dihydroxy-indole fluorimetric assay. Brit. J. Pharmacol. 48, 699–714 (1973)
Bertler, å., Carlsson, A., Rosengren, E.: A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta physiol. scand. 44, 273–292 (1958)
Blaschko, H., ChruŚciel, T. L.: The decarboxylation of amino acids related to tyramine and their awakening action in reserpine-treated mice. J. Physiol. (Lond.) 161, 272–284 (1960)
Carlsson, A.: Functional significance of drug-induced changes in brain monoamine levels. Progr. Brain Res. 8, 9–27 (1964)
Carlsson, A.: Drugs which block the storage of 5-hydroxytryptamine and related amines. In: Handbook of Experimental Pharmacology. Eichler, O. and Farah, A. eds. vol. 19, pp. 529–592. Berlin-Heidelberg-New York: Springer 1966
Carlsson, A., Lindqvist, M., Magnusson, T.: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature (Lond.) 180, 1200 (1957)
Carlsson, A., Waldeck, B.: A fluorimetric method for the determination of dopamine (3-hydroxytyramine). Acta physiol. scand. 44, 293–298 (1958)
Corrodi, H., Hanson, L. C. F.: Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia (Berl.) 10, 116–125 (1966)
Davies, J. A., Jackson, B., Redfern, P. H.: The effect of anti-parkinsonian drugs on haloperidol-induced inhibition of the conditioned-avoidance response in rats. Neuropharmacol. 12, 735–740 (1973)
Engel, J., Lundborg, P.: Regional changes in monoamine levels in the rate of tyrosine and tryptophan hydroxylation in 4 weeks old offspring of the nursing mothers treated with the neuroleptic drug penfluridol. Naunyn-Schmiedebergs Arch. Pharmacol. (In press 1974)
Everett, G. M., Toman, J. E. P.: Mode of action of Rauwolfia alkaloids and motor activity. Biol. Psychiatry 2, 75–81 (1959)
HÄggendal, J., Malmfors, T.: The effect of nerve stimulation on catecholamines taken up in adrenergic nerves after reserpine pretratment. Acta physiol. scand. 75, 33–38 (1969)
Magnusson, G., Corrodi, H., Hansson, E.: Renal lesions induced by α-methyl-tyrosine methylester and α-methyltyrosine. Acta pharmacol. (Kbh.) 28, 435–444 (1970)
Maj, J., Grabowska, M., Gajda, L.: Effect of apomorphine on motility in rats. Europ. J. Pharmacol. 17, 208–214 (1972)
Maj, J., Grabowska, M., Mogilnicka, E.: The effect of l-Dopa on brain catecholamines and motility in rats. Psychopharmacologia (Berl.) 22, 162–171 (1971)
Malmfors, T.: Studies on adrenergic nerves. Acta physiol. scand. 64, Suppl. 248, 58–61 (1965)
Moore, K. E., Dominic, J. A.: Tyrosine hydroxylase inhibitors. Fed. Proc. 30, 859–870 (1971)
Moore, K. E., Rech, R. H.: Reversal of α-methyl-tyrosine-induced behavioural depression with dihydroxyphenylalanine and amphetaime. J. Pharm. Pharmacol. 19, 405–407 (1967)
Moore, K. E., Wright, P. F., Bert, J. K.: Toxicological studies with α-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 155, 506–515 (1967)
Niemegeers, C. J. E., Verbruggen, F. J., Janssen, P. A. J.: The influence of various neuroleptic drugs on shock-avoidance responding in rats. Part I: Non-discriminated Sidman avoidance procedure. Psychopharmacologia (Berl.) 16, 161–174 (1969)
Porter, C. C., Watson, L. S., Titus, D. C., Totaro, J. A., Byer, S. S.: Inhibition of dopa decarboxylase by the hydrazino analog of α-methyldopa. Biochem. Pharmacol. 11, 1067–1077 (1962)
Schoenfeld, R. I., Seiden, L. S.: Effect of α-methyltyrosine on operant behavior and brain catecholamine levels. J. Pharmacol. exp. Ther. 167, 319–327 (1969)
Seiden, L. S., Carlsson, A.: Temporary and partial antagonism by l-3,4-dihydroxyphenylalanine of reserpine-induced suppression of a conditioned avoidance response. Psychopharmacologia (Berl.) 4, 418–423 (1963)
Siegel, S.: Nonparametric statistics for the behavioural sciences. New York: McGraw-Hill 1956
Smith, C. B., Dews, P. B.: Antagonism of locomotor suppressant effects of reserpine in mice. Psychopharmacologia (Berl.) 3, 55–59 (1962)
Van Orden, III, L. S., Bensch, K. G., Giarman, N. J.: Histochemical and functional relationships of catecholoamines in adrenergic nerve endings. II. Extravesicular norepinephrine. J. Pharmacol. exp. Ther. 155, 428–439 (1967)
Winer, B. J.: Statistical principles in experimental design. New York: McGraw-Hill 1962
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Ahlenius, S. Effects of low and high doses of l-Dopa on the tetrabenazine or α-methyltyrosine-induced suppression of behaviour in a successive discrimination task. Psychopharmacologia 39, 199–212 (1974). https://doi.org/10.1007/BF00421027
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DOI: https://doi.org/10.1007/BF00421027