Summary
Rats were injected daily with haloperidol, 0.5 mg/kg i.p. for a period of 16 days. 24 hours after the last injection of haloperidol these rats were challenged with gammabutyrolactone in doses of 200–750 mg/kg i.p.
The ensuing increase in neostriatal dopa-accumulation was significantly lower than in rats not previously treated with haloperidol. Since the increase in dopa-accumulation following GBL-treatment is most probably independent of postsynaptically located DA-receptors the difference between the experimental series is explained in terms of reduced feedback activation of DA-syrthesis due to the increased sensitivity of presynaptically located DA-autoreceptors.
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References
Andén, N.-E., Wachtel, H.: Increase in the turnover of brain dopamine by stimulation of muscarinic receptors outside the dopamine nerve terminals. J. Pharm. Pharmac.29, 435–437 (1977).
Carlsson, A., Kehr, W., Lindqvist, M., Magnusson, T., Atack, C. V.: Regultion of monoamine metabolism in the central nervous system. Pharmacol. Rev.24, 371–384 (1972).
Fjalland, B., Møller Nielsen, I.: Enhancement of methylphenidate-induced stereotypies by repeated administration of neuroleptics. Psychopharmacologia34, 105–109 (1974).
Gianutsos, G., Hynes, M. D., Lal, H.: Enhancement of apomorphine-induced inhibition of striatal dopamine-turnover following chror-haloperidol. Biochem. Pharmacol.24, 581–582 (1975).
Jackson, D. M., Andén, N.-E., Engel, J., Liljequist, S.: The effect of long term penfluridol treatment on the sensitivity of the dopamine receptor in the nucleus accumbens and in the corpus striatum. Psychopharmacologia45, 151–155 (1975).
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., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C. V.: Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol.24, 744–747 (1972).
Nowicky, M. C., Roth, R. H.: Presynaptic dopamine receptors. Development of supersensitivity following treatment with fluphenazine decanoate. Naunyn-Schmiedeberg's Arch. Pharmacol.300, 247–254 (1977).
Nowicky, M. C., Roth, R. H.: Dopaminergic neurons: role of presynaptic receptors in the regulation of transmitter biosynthesis. Prog. Neuro-Psychopharmac.2, 139–158 (1978).
Palkovits, M.: Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res.59, 449–450 (1973).
Sayers, A. C., Bürki, H. R., Ruch, W., Asper, H.: Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of clozapine, haloperidol, loxapine and chlorpromazine. Psychopharmacologia41, 97–104 (1975).
Scatton, B., Garrett, C., Julou, L.: Acute and subacute effects of neuroleptics on dopamine synthesis and release in the rat striatum. Naunyn-Schmiedeberg's Arch. Pharmacol.289, 419–434 (1975).
Stock, G., Magnusson, T., Andén, N.-E.: Increase in brain dopamine after axotomy or treatment with gammahydroxybutyric acid due to elimination of nerve impulse flow. Naunyn-Schmiedeberg's Arch. Pharmacol.278, 347–361 (1973).
Stock, G.: Failure of anticholinergic drugs to antagonize the increase in dopamine seen after gammahydroxybutyric acid and axotomy. J. Neural Transmission44, 137–143 (1979).
Tarsy, D., Baidessarini, R. J.: Pharmacologically induced behavioural supersensitivity to apomorphine. Nature New Biol.245, 262–263 (1973).
Udenfriend, S., Stein, S., Böhlen, P., Dairman, W., Leimgruber, W., Weigele, M.: Fluorescamine: a reagent for assay of amino acids, peptides, proteins, and primary amines in the picomole range. Science178, 871 to 872 (1972).
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Stock, G., Steinbrenner, J. & Kummer, P. Supersensitivity of dopamine-autoreceptors the effect of gammabutyrolactone in long-term haloperidol treated rats. J. Neural Transmission 47, 145–151 (1980). https://doi.org/10.1007/BF01670165
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DOI: https://doi.org/10.1007/BF01670165