Abstract
Mice, pretreated orally with l-DOPA (200 mg/kg) plus benserazide (50 mg/kg) (l-DOPA-B) responded when challenged 24h later with the same drug combination, with significantly greater locomotor stimulation than animals pretreated with the vehicle. The enhanced response was not due to an intrinsic effect of benserazide. Nor was it dependent on a change in central dopamine (DA) receptor sensitivity, because the two pretreatment groups (l-DOPA-B and vehicle) did not differ in their locomotor response to a range of apomorphine doses (300–3,000 μg/kg, IP). The enhanced response was, however, due to DA receptor stimulation because it was antagonised by premedication of the mice with haloperidol or pimozide. Moreover, the enhanced response to l-DOPA-B challenge was also produced when mice were pretreated (24h earlier) with a high dose of l-DOPA alone (without benserazide) (1,200 mg/kg, orally). Animals which had been pretreated with l-DOPA-B had significantly higher brain levels of l-DOPA and DA after a subsequent challenge dose of l-DOPA-B administered 24h later. Thus the enhanced response to l-DOPA-B observed in the present experiment appears to be dependent on some mechanism which produces higher concentrations of l-DOPA (and consequently DA) in the brain.
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References
Andén, N. E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Andén, N. E., Engel, J., Rubenson, A.: Mode of action of l-DOPA on central noradrenaline mechanisms. Naunyn-Schmiedeberg's Arch. Pharmacol. 273, 1–10 (1972)
Andén, N. E., Strömbom, U., Svensson, T. H.: Locomotor stimulation by l-DOPA: Relative importance of noradrenaline receptor activation. Psychopharmacology 54, 243–248 (1977)
Atack, C. V.: The determination of dopamine by a modification of the trihydroxyindole fluorimetric assay. Br. J. Pharmacol. 48, 699–714 (1973)
Atack, C., Magnusson, T.: A procedure for the isolation of noradrenaline (together with adrenaline), dopamine, 5-hydroxy-tryptamine and histamine from the same tissue sample using a single column of strongly acidic cation exchange resin. Acta Pharmacol. Toxicol. 42, 35–57 (1978)
Bailey, R. C., Jackson, D. M.: A pharmacological study of changes in central nervous system receptor responsivness after long-term dexamphetamine and apomorphine administration. Psychopharmacology 56, 317–326 (1978)
Bailey, R. C., Jackson, D. M., Bracs, P. U.: Long-term l-DOPA pretreatment of mice: Central receptor subsensitivity or supersensitivity. Psychopharmacology 66, 55–61 (1979)
Barbeau, A., Mars, H., Gillo-Joffroy, L.: Adverse clinical side effects of levodopa therapy. In: Parkinson's disease, McDowell, F. H., Markham, C. H. (eds.), pp. 203–237. Philadelphia: Davis 1971
Bartholini, G., Blum, J. E., Pletscher, A.: Dopa induced locomotor stimulation after inhibition of extracerebral decarboxylase. J. Pharm. Pharmacol. 21, 297–301 (1969)
Bartholini, G., Pletscher, A.: Decarboxylase inhibitors. Pharmacol. Ther. B. 1, 407–421 (1975)
Bianchine, J. R., Shaw, G. M.: Clinical pharmacokinetics of levodopa in Parkinson's disease. Clin. Pharmacokinetics 1, 313–338 (1976)
Butcher, L. L., Engel, J.: Behavioural and biochemical effects of l-DOPA after peripheral decarboxylase inhibition. Brain Res. 15, 233–242 (1969)
Coscia, C. J., Burke, W., Jamroz, G., Lasala, J. M., McFarlane, J., Mitchell, J., O'Toole, M. M., Wilson, M. L.: Occurrence of a new class of tetrahydroisoquinoline alkaloids in l-dopa-treated parkinsonian patients. Nature 269, 617–619 (1977)
Dairman, W., Christenson, J. G., Udenfriend, S.: Deorease in liver aromatic l-amino-acid decarboxylase produced by chronic administration of l-DOPA. Proc. Natl. Acad. Sci. USA 68, 2117–2120 (1971)
Dougan, D., Wade, D., Mearrick, P.: Agonist and antagonist effects of l-DOPA metabolites at a dopamine receptor suggest a pharmacological basis for the ‘on-off’ effect in Parkinson's disease. Nature 254, 70–71 (1975)
Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10, 316–323 (1967)
Kehr, W., Carlsson, A., Lindqvist, M.: A method for the determination of 3,4-dihydroxyphenylalanine (DOPA) in brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 273–280 (1972)
Kehr, W., Lindqvist, M., Carlsson, A.: Distribution of dopamine in the rat cerebral cortex. J. Neural Trans. 38, 173–180 (1976)
Klawans, H. L., Goetz, C., Nausieda, P. A., Weiner, W. J.: Levodopa-induced dopamine receptor hypersensitivity. Ann. Neurol. 2, 125–129 (1977)
Klawans, H. L., Margolin, D. I.: Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Arch. Gen. Psychiatry. 32, 725–732 (1975)
Sandler, M., Carter, S. B., Hunter, K. R., Stern, G. M.: Tetrahydroisoquinoline alkaloids: In vivo metabolites of l-DOPA in man. Nature 241, 439–443 (1973)
Segal, D. S., Mandell, A. J.: Long-term administration of d-amphetamine: Progressive augmentation of motor activity and stereotypy. Pharmacol. Biochem. Behav. 2, 249–255 (1974)
Sourkes, T. L.: Possible new metabolites mediating actions of l-DOPA. Nature 229, 413–414 (1971)
Steel, R. G. D., Torrie, J. H.: Principles and procedures of statistics. New York: McGraw-Hill 1960
Strömbom, U.: Catecholamine receptor agonists: Effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 167–176 (1976)
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Jenkins, O., Bailey, R., Crisp, E. et al. Subacute l-DOPA in mice: Biochemical and behavioural effects. Psychopharmacology 68, 77–83 (1980). https://doi.org/10.1007/BF00426654
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DOI: https://doi.org/10.1007/BF00426654