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The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats

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Summary

In the present experiment we tested the effects of L-DOPA and amphetamine upon dopamine and DOPAC efflux in vitro from superfused corpus striatal tissue fragments of male rats who had been pretreated with reserpine. Male rats were treated with reserpine (5mg/kg) or its vehicle at 24 hours prior to sacrifice and superfusion of the corpus striatum. Two different modes of L-DOPA (5 μM) and amphetamine (10 μM) stimulation, a brief 10-minute and a continuous 60-minute infusion, were tested for their ability to evoke striatal dopamine and DOPAC efflux. Depletion of monoamine storage capacity as achieved with reserpine significantly reduced the amount of basal dopamine and DOPAC released from superfused striatal tissue fragments of male rats. Although basal release rates were significantly reduced, the amount of dopamine and DOPAC released in response to in vitro L-DOPA infusions (10 or 60 minute infusions) was equivalent between reserpine and vehicle treated animals. In contrast, amphetamine stimulated DA release was significantly reduced in male rats treated with reserpine. For both L-DOPA and amphetamine, significantly greater amounts of dopamine were obtained with the 60-versus 10-minute infusion modes. These results demonstrate that the capacity for L-DOPA, but not amphetamine, to evoke dopamine efflux is unaltered under conditions when monoamine storage ability is diminished.

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References

  • Abercrombie ED, Bonatz AE, Zigmond MJ (1990) Effects of L-DOPA on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats. Brain Res 525: 36–44

    Google Scholar 

  • Algeri S, Achilli G, Calderini G, Perego C, Ponzio F, Toffano G (1987) Age-related changes in metabolic responses to chronic monoamine depletion in central dopaminergic and serotonergic systems of rats treated with reserpine. Neurobiol Aging 8: 61–66

    Google Scholar 

  • Bennett JP, Turk M, Landow E (1989) Continuous oral administration of L-dihydroxyphenylalanine (L-DOPA) solution to patients with advanced Parkinson's disease. Clin Neuropharmacol 12: 285–292

    Google Scholar 

  • Brannan T, Bhardwaj A, Martinez-Tica J, Weinberger J, Yahr M (1990) Striatal L-DOPA metabolism studied in vivo in rats with nigrostriatal lesions. J Neural Transm [PD-Sect] 2: 15–22

    Google Scholar 

  • Buu NT (1989) Vesicular accumulation of dopamine following L-DOPA administration. Biochem Pharmacol 38: 1787–1792

    Google Scholar 

  • Callaway CW, Kuczenski R, Segal DS (1989) Reserpine enhances amphetamine stereotypies without increasing amphetamine-induced changes in striatal dialysate dopamine. Brain Res 505: 83–90

    Google Scholar 

  • Chase TN, Baronti F, Falbrine G, Heuser IJ, Juncos JL, Mouradian MM (1989) Rationale for continuous dopaminergic therapy of Parkinson's disease. Neurology 39 [Suppl2]: 7–10

    Google Scholar 

  • Carlsson A (1966) Drugs which block the storage of 5-hydroxytryptamine and related amines. In: Esparmer V (ed) Handbook of experimental pharmacology. Springer, Berlin Heidelberg New York, pp 529–592

    Google Scholar 

  • Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180: 1200

    Google Scholar 

  • Colpaert FC (1987) Pharmacological characteristics of tremor, rigidity and hypokinesia induced by reserpine in rat. Neuropharmacology 26: 1431–1440

    Google Scholar 

  • Cooper DR, Marrel C, Van de Waterbeemd H, Testa B, Jenner P, Marsden CH (1987) L-DOPA esters as potential prodrugs: behavioral activity in experimental models of Parkinson's disease. J Pharm Pharmacol 39: 627–635

    Google Scholar 

  • Cooper DR, Marrel C, Van de Waterbeemd H, Testa B, Jenner P, Marsden CD (1987) L-DOPA esters as potential prodrugs: effect on brain concentration of dopamine metabolites in reserpinized mice. J Pharm Pharmacol 39: 809–818

    Google Scholar 

  • Curzon G (1990) How reserpine and chlorpromazine act: the impact of key discoveries on the history of psychopharmacology. TIPS 11: 61–63

    Google Scholar 

  • Dluzen DE, Kratko Jr FT (1992) L-DOPA infusion mode differentially affects corpus striatal dopamine efflux in the presence of reserpine. J Neural Transm [Gen Sect] 89: 197–207

    Google Scholar 

  • Dluzen DE, McDermott JL, Ramirez VD (1991) Changes in dopamine release in vitro from the corpus striatum of young versus aged rats as a function of infusion modes of L-DOPA, potassium and amphetamine. Exp Neurol 112: 153–160

    Google Scholar 

  • Dluzen D, Jain R, Liu B (1994) Modulatory effects of testosterone upon 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. J Neurochem (in press)

  • Duvoisin R (1987) History of parkinsonism. Pharmacol Ther 32: 1–17

    Google Scholar 

  • Elverfors A, Nissbrandt H (1991) Reserpine-insensitive dopamine release in the substantia nigra? Brain Res 557: 5–12

    Google Scholar 

  • Engber TM, Susel Z, Juncos JL, Chase TN (1989) Continuous and intermittent levodopa differentially affect rotation induced by D-l and D-2 dopamine agonists. Eur J Pharmacol 16: 291–298

    Google Scholar 

  • Fornstedt B, Carlsson A (1989) A marked rise in 5-S-cysteinyl levels in guinea-pig striatum following reserpine treatment. J Neural Transm 76: 155–161

    Google Scholar 

  • Gauthier S, Amyot D (1992) Sustained release of antiparkinson agents: controlled release levodopa. Can J Neurol Sci 19: 153–155

    Google Scholar 

  • Goshima Y, Misu Y, Arai N, Misugi K (1991) Nanomolar L-DOPA facilitates release of dopamine via presynaptic β-adrenoceptors: comparative studies on the actions in striatal slices from control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated C 57 black mice, an animal model for Parkinson's disease. Jpn J Pharmacol 55: 93–100

    Google Scholar 

  • Hornykiewcz O (1974) The mechanism of action of L-DOPA in Parkinson's disease. Life Sci 15: 1249–1259

    Google Scholar 

  • Hornykiewcz O (1983) Dopamine changes in the aging human brain: functional considerations. In: Agnoli A, Crepaldi G, Spano PF, Trabucchi M (eds) Aging, vol 23. Raven Press, New York, pp 9–14

    Google Scholar 

  • Juncos JL, Engber TM, Raisman R, Thirbout F, Ploska A, Agid Y, Chase TN (1989) Continuous and intermittent levodopa differentially affect basal ganglia function. Ann Neurol 25: 473–478

    Google Scholar 

  • Leenders KL, Palmer AJ, Quinn N, Clark JC, Firnau G, Garrett ES, Nahmias C, Jones T, Marsden CD (1986) Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography. J Neurol Neurosurg Psychiatry 49: 853–860

    Google Scholar 

  • Lieberman A (1988) Dopamine agonists: new perspectives. Neuro View 4: 1–20

    Google Scholar 

  • Lieberman A (1992) Long-term experience with selegiline and levodopa in Parkinson's disease. Neurology 42 [Suppl4]: 32–35

    Google Scholar 

  • Lytle LD, Hurko O, Romero JA, Cottman K, Leehy D, Wurtman RJ (1972) The effects of 6-hydroxydopamine pretreatment on the accumulation of DOPA and dopamine in brain and peripheral organs following L-DOPA administration. J Neural Transm 33: 63–72

    Google Scholar 

  • Marsden CD (1980) “On-Off” phenomena in Parkinson's disease. In: Rinne UK, Klingler M, Stamm G (eds) Parkinson's disease: current progress, problems in management. Elsevier North Holland, Amsterdam New York, pp 241–254

    Google Scholar 

  • Melamed E (1987) The failing efficacy of long-term levodopa therapy in Parkinson's disease. I. Chemical features and neurochemical mechanisms. Neuro View 3: 1–16

    Google Scholar 

  • Melamed E (1990) Interactions of exogenous L-DOPA with nigrostriatal dopaminergic neurons in Parkinson's disease. Adv Neurol 53: 61–66

    Google Scholar 

  • Misu Y, Goshima Y, Kubo T (1986) Biphasic actions of L-DOPA on the release of endogenous dopamine via presynaptic receptors in rat striatal slices. Neurosci Lett 72: 194–198

    Google Scholar 

  • Mouradian MM, Heuser IJE, Baronti F, Chase TN (1990) Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease. Ann Neurol 27: 18–23

    Google Scholar 

  • Ng KY, Chase TN, Colburn RW, Kopin IJ (1970) L-DOPA-induced release of cerebral monoamines. Science 170: 76–77

    Google Scholar 

  • Niddam R, Arbilla S, Scatton B, Dennis T, Langer SZ (1985) Amphetamine-induced release of endogenous dopamine in vitro is not reduced following pretreatment with reserpine. Naunyn Schmiedebergs Arch Pharmacol 329: 123–127

    Google Scholar 

  • Ofori S, Bretton C, Hof P, Schorderet M (1986) Investigation of dopamine content, synthesis, and release in the rabbit retina in vitro. I. Effects of dopamine precursors, reserpine, amphetamine, and L-DOPA decarboxylase and monoamine oxidase inhibitors. J Neurochem 47: 1199–1206

    Google Scholar 

  • Pasinetti GM, Morgan DG, Johnson SA, Millar SL, Finch CE (1990) Tyrosine hydroxylase mRNA concentration in midbrain dopaminergic neurons is differentially regulated by reserpine. J Neurochem 55: 1793–1799

    Google Scholar 

  • Ramirez VD, Kim K, Dluzen D (1985) Progesterone action on the LHRH and nigrostriatal dopamine neuronal systems: in vitro and in vivo studies. In: Greep RO (ed) Recent progress in hormone research, vol 41. Academic Press, Orlando, pp 421–472

    Google Scholar 

  • Sourkes TL (1961) Formation of dopamine in vivo: relation to the function of the basal ganglia. Rev Can Biol 20: 187–196

    Google Scholar 

  • Spencer SE, Wooten GF (1984) Altered pharmacokinetics of L-DOPA metabolism in rat striatum deprived of dopaminergic innervation. Neurology 34: 1105–1108

    Google Scholar 

  • Starr BA, Starr MS, Kilpatrick IC (1987) Behavioral role of dopamine d1 receptors in the reserpine-treated mouse. Neuroscience 22: 179–188

    Google Scholar 

  • Synder GL, Zigmond MJ (1990) The effects of L-DOPA on in vitro dopamine release from the striatum. Brain Res 508: 181–187

    Google Scholar 

  • Tyce GM, Rorie DK (1985) Effect of L-DOPA and L-tyrosine on release of free and conjugated dopamine, homvanillic acid and dihydroxyphenyl-acetic acid from slices of rat striatum. Life Sci 37: 2439–2448

    Google Scholar 

  • Uretsky NJ, Snodgrass SR (1977) Studies on the mechanism of stimulation of dopamine synthesis by amphetamine in striatal slices. J Pharmacol Exp Ther 202: 565–580

    Google Scholar 

  • van Horne C, Hoffer BH, Stromberg I, Gerhardt GA (1992) Clearance and diffusion of locally applied dopamine in normal and 6-hydroxydopamine-lesioned rat striatum. J Pharmacol Exp Ther 263: 1285–1292

    Google Scholar 

  • Weick BG, Engber TM, Susel Z, Chase TN, Walters JR (1990) Responses of substantia nigra pars reticulata neurons to GABA and SKF 38393 in 6-hydroxydopamine-lesioned rats are differentially affected by continuous and intermittent levodopa administration. Brain Res 523: 16–22

    Google Scholar 

  • Zetterström T, Herrera-Marcshitz M, Ungerstedt U (1986) Simultaneous measurement of dopamine release and rotational behavior in 6-hydroxydopamine denervated rats using intracerebral dialysis. Brain Res 376: 1–7

    Google Scholar 

  • Zigmond MJ, Abercrombie ED, Stricker EM (1990) Partial damage to nigrostriatal bundle: compensatory changes and the action of L-DOPA. J Neural Transm [Suppl] 29: 217–232

    Google Scholar 

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Dluzen, D.E., Liu, B. The effect of reserpine treatment in vivo upon L-dopa and amphetamine evoked dopamine and DOPAC efflux in vitro from the corpus striatum of male rats. J. Neural Transmission 95, 209–222 (1994). https://doi.org/10.1007/BF01271567

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