Summary
Tritium accumulation during incubation with 3-H-choline, and the efflux as well as the electrically evoked overflow of tritium during subsequent superfusion, were investigated in slices from unilateral striatal suspension grafts 16 to 20 weeks after implantation into the previously ibotenic acid-lesioned rat striatum. Slices from non-operated animals, from striata contralateral to grafts, and from animals with acute ibotenic acid lesions of the striatum were studied in parallel. The accumulation of tritium and the overflow of tritium in response to electrical stimulation (2 min, 3 Hz) were markedly impaired in acutely lesioned striata. In graft slices, tritium accumulation and the subsequent electrically evoked overflow were greater than in slices obtained after acute lesions, but were still smaller than in non-operated animals or in the contralateral striata. The dopamine D2-receptor agonist quinpirole inhibited the electrically evoked overflow of tritium in grafts, but only to a small extent. The D2-receptor antagonist sulpiride increased, whereas the dopamine uptake inhibitor nomifensine and the dopamine releasing drug amphetamine decreased the evoked overflow in slices from non-operated rats and from striata contralateral to grafts, but had no significant effect in grafts. As in graft slices, the release of acetylcholine in striata from animals in which the mesostriatal dopamine pathway had been lesioned by 6-hydroxy-dopamine was not changed by sulpiride and amphetamine, and was only minimally decreased by nomifensine. Our data show that striato-striatal grafts can partly restore the impaired choline accumulation and acetylcholine release in excitotoxinlesioned striata. Functional D2-receptors are present on graft cholinergic cells, but are not activated by endogenous dopamine under the present in vitro conditions.
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Baud P, Arbilla S, Langer SZ (1985) Inhibition of the electrically evoked release of [3H]acetylcholine in rat striatal slices: an experimental model for drugs that enhance dopaminergic neurotransmission. J Neurochem 44:331–337
Brundin P, Isacson O, Björklund A (1985) Monitoring of cell viability in suspensions of embryonic CNS tissue and it use as a criterion for intracerebral graft survival. Brain Res 331:251–259
Chesselet MF (1984) Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis. Neuroscience 12:347–375
Clarke DJ, Dunnett SB, Isacson O, Sirinathsinghji DJS, Björklund A (1988) Striatal grafts in rats with unilateral neostriatal lesions. I. Ultrastructural evidence of afferent synaptic inputs from host nigrostriatal pathway. Neuroscience 24:791–801
Coyle JT, Schwarcz R (1983) The use of excitatory amino acids as selective neurotoxins. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 1. Elsevier, Amsterdam, pp 508–527
Cubeddu LX, Hoffmann IS (1983) Frequency-dependent release of acetylcholine and dopamine from rabbit striatum: its modulation by dopaminergic receptors. J Neurochem 41:94–101
Deckel AW, Robinson RG, Coyle JT, Sanberg PR (1983) Reversal of long-term locomotor abnormalities in the kainic acid model of Huntington's disease by day 18 fetal striatal implants. Eur J Pharmacol 93:287–288
Deckel AW, Robinson RG (1987) Receptor characteristics and behavioral consequences of kainic acid lesions and fetal transplants of the striatum. In: Azmita EC, Björklund A (eds). Ann NY Acad Sci 495:508–527
Dunnett SB, Isacson O, Sirinathsinghji DJS, Clarke DJ, Björklund A (1988) Striatal grafts in rats with unilateral neostriatal lesions. III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching. Neuroscience 24:813–820
Hadházy P, Szerb JC (1977) The effect of cholinergic drugs on [3H] acetylcholine release from slices of rat hippocampus, striatum and cortex. Brain Res 123:311–322
Helmreich I, Reimann W, Hertting G, Starke K (1982) Are presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in the rabbit caudate nucleus pharmacologically different? Neuroscience 7:1559–1566
Hertting G, Zumstein A, Jackisch R, Hoffmann I, Starke K (1980) Modulation by endogenous dopamine of the release of acetylcholine in the caudate nucleus of the rabbit. NaunynSchmiedeberg's Arch Pharmacol 315:111–117
Hoffmann IS, Talmaciu RK, Cubeddu LX (1986) Interactions between endogenous dopamine and dopamine agonists at release modulatory receptors: multiple effects of neuronal uptake inhibitors on transmitter release. J Pharmacol Exp Ther 238:437–446
Isacson O, Brundin P, Kelly PAT, Gage FH, Björklund A (1984) Functional neuronal replacement by grafted striatal neurones in the ibotenic acid-lesioned rat striatum. Nature 311:458–460
Isacson O, Brandin P, Gage FH, Björklund A (1985) Neural grafting in a rat model of Huntington's disease: progressive neurochemical changes after neostriatal ibotenate lesions and striatal tissue grafting. Neuroscience 16:799–817
Isacson O, Dawbarn D, Brundin P, Gage FH, Emson PC, Björklund A (1987) Neural grafting in a rat model of Huntington's disease: striosomal-like organization of striatal grafts as revealed by acetylcholinesterase histochemistry, immunocytochemistry and receptor autoradiography. Neuroscience 22:481–497
Joyce JN, Marshall JF (1987) Quantitative autoradiography of dopamine D2 sites in rat caudate-putamen: localization to intrinsic neurons and not to neocortical afferents. Neuroscience 20:773–795
McAllister JP, Walker PD, Chowanas GI (1987) Transplants of neostriatal primordia contain acetylcholinesterase-positive neurons. In: Azmita EC, Björklund A (eds). Ann NY Acad Sci 495:508–527
Nieoullon A, Chéramy A, Glowinski J (1977) Interdependence of the nigrostriatal dopaminergic systems on the two sides of the brain in the cat. Science 238:416–418
Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, Sydney
Pritzel M, Isacson O, Brundin P, Wiklund L, Björklund A (1986) Afferent and efferent connections of striatal grafts implanted into the ibotenic acid lesioned neostriatum in adult rats. Expl Brain Res 65:112–116
Richardson IW, Szerb JC (1974) The release of labelled acetylcholine and choline from cerebral cortical slices stimulated electrically. Br J Pharmacol 52:499–507
Schmidt RH, Ingvar M, Lindval O, Stenevi U, Björklund A (1982) Functional activity of substantia nigra grafts reinnervating the striatum: neurotransmitter metabolism and [14C]2-deoxy-d-glucose autoradiography. J Neurochem 38:737–748
Sirinathsinghji DJS, Dunnett SB, Isacson O, Clarke DJ, Kendrick K, Björklund A (1988) Striatal grafts in rats with unilateral neostriatal lesions. II. In vivo monitoring of GABA release in globus pallidus and substantia nigra. Neuroscience 24:803–811
Stoof JC, Thieme RE, Vrijmoed-de Vries MC, Mulder AH (1979) In vitro acetylcholine release from rat caudate nucleus as a new model for testing drugs with dopamine-receptor activity. Naunyn-Schmiedeberg's Arch Pharmacol 309:119–124
Wictorin K, Isacson O, Fischer W, Nothias F, Pechanski M, Björklund A (1988) Connectivity of striatal grafts implanted into the ibotenic acid lesioned striatum. I. Subcortical afferents. Neuroscience (in press)
Wuerthele SM, Lovell KL, Jones MZ, Moore KE (1978) A histological study of kainic acid-induced lesions in the rat brain. Brain Res 149:489–497
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Wichmann, T., Wictorin, K., Björklund, A. et al. Release of acetylcholine and its dopaminergic control in slices from striatal grafts in the ibotenic acid-lesioned rat striatum. Naunyn-Schmiedeberg's Arch Pharmacol 338, 623–631 (1988). https://doi.org/10.1007/BF00165626
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DOI: https://doi.org/10.1007/BF00165626