Summary
In the present study the functional role of the striato-nigral dynorphin and substance P pathways in rat brain has been studied using the rotational behavioural model and an intracerebral dialysis technique complemented with brain lesions and immunohistochemical analysis. Attempts were made to evaluate whether these striato-nigral neurons have a feed-back modulatory action on the dopaminergic nigro-striatal system, or whether they represent an outflow pathway conveying motor information from the striatum. Unilateral injection of dynorphin A into the substantia nigra reticulata of naive rats induced contralateral rotational behaviour. This effect was dose-dependent and mimicked by the kappa-opioid receptor agonist, U50,488H. Intranigral injection of substance P, as well as substance K, also produced dose-dependent contralateral rotational behaviour. Unilateral injections of ibotenic acid into various sites of the striatum were used to destroy the striato-nigral pathways. The lesions produced a depletion of dynorphin- and substance P-like immunoreactivity in the pars reticulata of the substantia nigra ipsilateral to the lesion and markedly affected the behavioural responses to intranigral peptide injections. Dynorphin A more potently induced contralateral rotation in the lesioned compared to naive non-lesioned rats, suggesting development of supersensitivity for this peptide. Substance P on the other hand, was markedly less potent in inducing rotation in lesioned animals. The rotational responses to both dynorphin A and substance P were potentiated by injection of amphetamine 1 h later, suggesting that both peptides act via nigro-striatal dopamine neurons. However, in rats with unilateral nigro-striatal dopamine denervation, produced with 6-hydroxy-dopamine, dynorphin A retained its potency to induce rotational behaviour; substance P was again much less potent. Thus, both the ibotenic acid and 6-hydroxy-dopamine lesions differently affect the action of dynorphin A and substance P in the zona reticulata of the substantia nigra. The data suggests that substance P requires an intact dopamine pathway to produce the rotational response, while dynorphin A does not. Direct evidence that behavioural activation produced by dynorphin A is not dependent upon dopamine stimulation was obtained by intrastriatal dialysis experiments in which changes in striatal dopamine release were measured following intranigral injection of dynorphin A or substance P. Intranigral dynorphin A in fact reduced, while substance P increased the release of dopamine. It is concluded that the dynorphin and substance P striatonigral pathways have different functions. Thus, substance P in the striato-nigral pathway may have a role in a positive feed-back loop regulating the firing of nigro-striatal dopamine neurons, while dynorphin might be important in negative feed-back control. The rotational behaviour produced by DYN A is probably due to direct stimulation of receptors located on nigro-thalamic and nigro-tectal pathways.
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Anden NE, Dahlström A, Fuxe K, Larsson K, Olson L, Ungerstedt U (1966) Ascending monoamine neurons to the telencephalon and diencephalon. Acta Physiol Scand 67: 313–326
Anden N-E, Stock G (1973) Inhibitory effect of gammahydroxybutyric acid and gammaaminobutyric acid on the dopamine cells in the substantia nigra. Naunyn-Schmiedeberg's Arch Pharmacol 279: 89–92
Anden N-E (1974) Inhibition of the turnover of the brain dopamine after treatment with gammaaminobutyrate: 2-oxyglutarate transaminase inhibitor aminooxyacetic acid. Naunyn-Schmiedeberg's Arch Pharmacol 283: 419–424
Aronin N, DiFiglia M, Graveland GA, Schwartz WJ, Wu J-Y (1984) Localization of immunoreactive enkephalins in GABA synthesizing neurons of the rat neostriatum. Brain Res 300: 376–380
Brodin E, Lindefors N, Dalsgaard C-J, Theodorsson E, Rosell S (1985) Tachykinin multiplicity in rat nervous system as studied using antisera raised against substance P and neurokinin A. Regulatory Peptides 13: 263–282
Brookes A, Bradley PB (1984) Electrophysiological evidence for K-agonist activity of dynorphin in rat brain. Neuropharmacology 23: 207–210
Brownstein MJ, Mroz EA, Tappaz ML, Leeman SE (1977) On the origin of substance P and glutamic decarboxylase (GAD) in the substantia nigra. Brain Res 135: 315–323
Bunney BS, Aghajanian GK (1976a) D-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striatonigral feedback pathway. Science 192: 391–393
Bunney BS, Aghajanian GK (1976b) Dopaminergic influence in the basal ganglia: evidence for striatonigral feedback regulation. In: Yahr MD (ed) Basal ganglia. Raven Press, New York, pp 249–267
Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytryptamine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 20: 140–144
Cheramy A, Nieoullon A, Michelet R, Glowinski J (1977) Effects of intranigral application of dopamine and substance P on the in vivo release of newly synthetized (3H)dopamine in the ipsilateral caudate nucleus of the rat. Neurosci Lett 4:105–109
Chevalier G, Thierry AM, Shibazaki T, Feger J (1981) Evidence for a GABAergic inhibitory nigrotectal pathway in the rat. Neurosci Lett 21: 67–70
Christensson-Nylander I, Terenius L (1985) Dynorphin peptides in the human substantia nigra. Neuropeptides 6: 391–396
Christensson-Nylander I, Herrera-Marschitz M, Staines W, Hökfelt T, Terenius L, Ungerstedt U, Cuello C, Oertel W, Goldstein M (1986) Striato-nigral dynorphin and substance P pathways in the rat. I. Biochemical and immunohistochemical studies. Exp Brain Res 64: 169–192
Collinridge GL, Davies J (1982) Actions of substance P and opiates in the rat substantia nigra. Neuropharmacology 21: 715–719
Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurones. Acta Physiol Scand 62 (Suppl 232): 1–55
Davies J, Dray A (1976) Substance P in the substantia nigra. Brain Res 107: 623–627
Dores RM, Lewis ME, Khachaturian H, Watson SJ, Akil H (1985) Analysis of opioid and non-opioid end products of prodynorphin in the substantia nigra of the rat. Neuropeptides 5: 501–504
Dray A (1979) The striatum and the substantia nigra: a commentary on their relationships. Neuroscience 4: 1407–1439
Fallon JH, Leslie FM, Cone RI (1985) Dynorphin-containing pathways in the substantia nigra and ventral tegmentum: double labeling study using combined irnmunofluorescence and retrograde tracing. Neuropeptides 5: 457–460
Gale K, Hong JS, Guidotti A (1977) Presence of substance P and GABA in separate striatonigral neurons. Brain Res 136: 371–375
Gerfen CR (1985) The neostriatal mosaic. I. Compartmental organization of projections from the striatum to the substantia nigra in the rat. Comp Neurol 236: 454–476
Glowinski J, Torrens Y, Beaujovan JC (1982) The striatonigral substance P pathway and dopaminergic mechanisms. In: CIBA Foundation Symposium 91. Substance P in the nervous system. Pitman, London, pp 281–295
Goldstein A, Tachibana S, Lowney LI, Hunkapiller M, Hood L (1979) Dynorphin-(1–13), an extraordinary potent opioid peptide. Proc Natl Acad Sci USA 76: 6666–6670
Goldstein A, Fischli W, Lowney LI, Hunkapiller M, Hood L (1981) Porcine pituitary dynorphin: complete amino acid sequence of the biologically active heptadecapeptide. Proc Natl Acad Sci USA 78: 7219–7223
Grace AA, Bunney BS (1979) Paradoxical GABA excitation of nigral dopaminergic cells: indirect mediation through reticulata inhibitory neurons. Eur J Pharmacol 59: 211–218
Gramsch C, Höllt V, Pasi A, Mehraein P, Herz A (1982) Immunoreactive fibers and terminals in the monkey central nervous system: an immunohistochemical study. Neuroscience 7: 1049–1095
Groves PM, Wilson CJ, Young SJ, Rebec GV (1975) Selfinhibition by dopaminergic neurons. Science 190: 522–529
Herrera-Marschitz M, Hökfelt T, Ungerstedt U, Terenius L (1983) Functional studies with the opioid peptide dynorphin: acute effects of injections into the substantia nigra reticulata of naive rats. Life Sci 33: 555–558
Herrera-Marschitz M, Ungerstedt U (1984a) Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1 and D2 receptor sites. Eur J Pharmacol 98: 165–176
Herrera-Marschitz M, Ungerstedt U (1984b) Evidence that striatal efferents relate to different dopamine receptors. Brain Res 323: 269–278
Herrera-Marschitz M, Hökfelt T, Ungerstedt U, Terenius L, Goldstein M (1984a) Effect of intranigral injections of dynorhin, dynorphin fragments and α-neoendorphin on rotational behaviour in the rat. Eur J Pharmacol 102: 213–227
Herrera-Marschitz M, Hökfelt T, Terenius L, Ungerstedt U (1984b) Dopamine-dynorphin interactions in striato-nigral pathways of rats. Proceedings of the 14th Int CINP Congress in Florence. Fidia Research Biomedical Information, Italy, pp 942
Herrera-Marschitz M, Forster C, Ungerstedt U (1985a) Rotational behaviour elicited by intracerebral injections of apomorphine and pergolide in 6-hydroxy-dopamine-lesioned rats. I. Comparison between systemic and intrastriatal injections. Acta Physiol Scand 125: 519–527
Herrera-Marschitz M, Forster C, Ungerstedt U (1985b) Rotational behaviour elicited by intracerebral injections of apomorphine and pergolide in 6-hydroxy-dopamine-lesioned rats. II. The striatum of the rat is heterogeneously organized for rotational behaviour. Acta Physiol Scand 125: 529–535
Hong JS, Yang HY, Racagni G, Costa E (1977) Projections of substance P containing neurons from neostriatum to substantia nigra. Brain Res 122: 541–544
Hökfelt T, Johansson O, Kellerth J-O, Ljungdahl Å, Nilsson G, Nygård A, Pernow B (1977) Immunohistochemical distribuion of substance P. In: Von Euler US, Pernow B (eds) Substance P. Nobel Symposium 37. Raven Press, New York, pp 117–145
Hökfelt T, Vincent SR, Dalsgaard CJ, Herrera-Marschitz M, Ungerstedt U, Schultzberg M, Christensson I, Terenius L (1984) Some aspects on distribution and role of opioid peptides in the central and peripheral nervous system. In: Müller EE, Genazzani AP (eds) Central and peripheral endorphins: basic and clinical aspects. Raven Press, New York, pp 1–16
Innis RB, Andrade R, Aghajanian GK (1985) Substance K excites dopaminergic and non-dopaminergic neurons in rat substantia nigra. Brain Res 335: 381–383
James TA, Star MS (1977) Behavioural and biochemical effects of substance P injected into the substantia nigra of the rat. J Pharm Pharmacol 29: 181–182
James TA, Starr MS (1978) The role of GABA in the substantia nigra. Nature 275: 229–230
James TA, Starr MS (1979) Effects of substance P injected into the substantia nigra. Br J Pharmacol 65: 423–429
Jessell TM (1978) Substance P release from the rat substantia nigra. Brain Res 151: 469–478
Jessell T, Iversen LL, Kanazawa I (1976) Release and metabolism of substance P in rat hypothalamus. Nature 264: 81–83
Jessell TM, Emson PC, Paxinos G, Cuello AC (1978) Topographic projections of substance P and GABA pathways in the striato- and pallido-nigral system: a biochemical and immunohistochemical study. Brain Res 152: 487–498
Kalivas PW, Deutch AY, Maggio JE, Mantyh PW, Roth RH (1985) Substance K and substance P in the ventral tegmental area. Neurosci Lett 57: 241–246
Kangawa K, Hinamino N, Fukada A, Matsuo H (1983) Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Comm 114: 533–540
Kanazawa I, Emson PC, Cuello C (1977) Evidence for the existence of substance P containing fibers in striato-nigral and pallido-nigral pathways in rat brain. Brain Res 119: 447–453
Kanazawa I, Ogawa T, Kimura S, Munekata E (1984) Regional distribution of substance P, neurokinin alpha and neurokinin beta in rat central nervous system. Neurosci Res 2: 111–120
Kelley AE, Cador M, Stinus L (1985) Behavioural analysis of the effect of substance P injected into the ventral mesencephalon on investigatory and spontaneous motor behavior in the rat. Psychopharmacology 85: 37–46
Kilpatrick IC, Collinridge GL, Starr MS (1982) Evidence for the participation of nigrotectal gamma-aminobutyrate-containing neurons in striatal and nigral-derived circling in the rat. Neuroscience 7: 207–222
Kimura S, Okada M, Sugita Y, Kanazawa I, Munekata E (1983) Novel neuropeptides, neurokinin α and β isolated from porcine spinal cord. Proc Jpn Acad 59B: 101–104
Kohno J, Shiosaka S, Shinoda K, Inagaki S, Tohyama M (1984) Two distinct strio-nigral substance P pathways in the rat: an experimental immunohistochemical study. Brain Res 308: 309–317
König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. R E Krieger Publishing Co Inc, New York
Li CH (1985) β-endorphins: some aspects of structure-function relationship. In: Müller EE, Genazzani AR (eds). Central and peripheral endorphins: basic and clinical aspects. Raven Press, New York, pp 17–26
Lindefors N, Brodin E, Theodorsson-Norheim E, Ungerstedt U (1985) Regional distribution and in vivo release of tachykinin-like immunoreactivity in rat brain: evidence for regional differences in relative proportions of tachykinins. Regulatory Peptides 10: 217–230
Lindvall O, Björklund A (1974) The organization of the ascending catecholamine neuron systems in the rat brain as revealed by the glyoxylic acid fluorescence method. Acta Physiol Scand Suppl 412: 1–48
Ljungdahl Å, Hökfelt T, Nilsson G (1978a) Distribution of substance P-like immunoreactivity in the central nervous system in the rat. I. Cell bodies and nerve terminals. Neuroscience 3: 861–943
Ljungdahl Å, Hökfelt T, Nilsson G, Goldstein M (1978b) Distribution of substance P-like immunoreactivity in the central nervous system in the rat. II. Light microscopic localization in relation to catecholamine-containing neurons. Neuroscience 3: 945–976
Lundberg JM, Hökfelt T, Änggård A, Terenius L, Markey K, Goldstein M (1982) Organization principles in the peripheral sympathetic nervous system: subdivisions by coexisting peptides (somatostatin, avian pancreatic polypeptide and vasoactive intestinal polypeptide-like immunoreactive material). Proc Natl Acad Sci USA 79: 1300–1307
Maggio JE, Hunter JC (1984) Regional distribution of kassinin-like immunoreactivity in rat central and peripheral tissues and the effect of capsaicin. Brain Res 307: 370–373
Mantyh PW, Maggio JE, Hunt SP (1984) The autoradiographic distribution of kassinin and substance K binding sites is different from the distribution of substance P binding sites in rat brain. Eur J Pharmacol 102: 361–364
Maysinger D, Höllt V, Seizinger BR, Mehraein P, Pasi A, Herz A (1982) Parallel distribution of immunoreactive α-neoendorphin and dynorphin in rat and human tissue. Neuropeptides 2: 211–225
McGeer EG, Staines WA, McGeer PL (1984) Neurotransmitters in the basal ganglia. Can J Neurol Sci Suppl 11: 89–99
Michelot R, Leviel V, Giorguieff-Chesselet MF, Cheramy A, Glowinski J (1979) Effects of the unilateral nigral modulation of SP transmission on the activity of the two nigro-striatal dopaminergic pathways. Life Sci 24: 715–724
Minamino N, Kangawa K, Fukuda A, Matsuo H (1984) A novel mammalian tachykinin identified in porcine spinal cord. Neuropeptides 4: 157–166
Morelli M, Di Chiara G (1985) Non-dopaminergic mechanisms in the turning behaviour evoked by intranigral opiates. Brain Res 341: 350–359
Nawa H, Hirose T, Takashima H, Inayama S, Nakanishi S (1983) Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature 306: 32–36
Nissbrandt H, Pileblad E, Carlsson A (1985) Evidence for dopamine release and metabolism beyond the control of nerve impulses and dopamine receptors in rat substantia nigra. J Pharm Pharmacol 37: 884–889
Oertel WH, Riethmuller G, Mugnaini E, Schmechel DA, Weindl A, Gramsch C, Herz A (1983) Opioid peptide like immunoreactivity in GABAergic neurons of rat neostriatum and central amygdaloid nucleus. Life Sci Suppl I 33: 76–79
Olpe HR, Koella WP (1977) Rotatory behaviour in rats by intranigral application of substance P and an eledoisin fragment. Brain Res 126: 576–579
Paterson SJ, Robson LE, Kosterlitz HW (1983) Classification of opioid receptors. Br Med Bull 39: 31–36
Pearse A, Polak JM (1975) Bifunctional reagents as vapour and liquid-phase fixatives for immunohistochemistry. Histochem J 7: 179–186
Pinnock RD, Dray A (1982) Differential sensitivity of presumed dopaminergic and non-dopaminergic neurons in rat substantia nigra to electrophoretically applied substance P. Neurosci Lett 29: 153–158
Pittius CW, Seizinger BR, Pasi A, Mehraein P, Herz A (1984) Distribution and characterization of opioid peptides derived from proenkephalin A in human and rat central nervous system. Brain Res 304: 127–136
Quirion R, Dam TV (1985) Multiple tachykinin receptors in guinea pig brain. High densities of substance K (Neurokinin A) binding sites in the substantia nigra. Neuropeptides 6: 191–204
Quirion R, Gaudreau P, Martel J-C, St-Pierre S, Zamir N (1985) Possible interactions between dynorphin and dopaminergic systems in rat basal ganglia and substantia nigra. Brain Res 331: 358–362
Quirion R, Than-Vinh D (1985) Multiple tachykinin receptors. In: Jordan CC, Oehme P (eds) Substance P: metabolism and biological actions. Taylor & Francis, London, pp 45–64
Sakurada T, Le Greves P, Stewart J, Terenius L (1985) Measurement of substance P metabolites in rat CNS. J Neurochem 44: 718–722
Schenker C, Mroz EA, Leeman SE (1976) Release of substance P from isolated nerve endings. Nature 264: 790–792
Schwarcz R, Hökfelt T, Fuxe K, Jonsson G, Goldstein M, Terenius L (1979) Ibotenic acid-induced neuronal degeneration: a morphological and neurochemical study. Exp Brain Res 37: 199–216
Sharp T, Zetterström T, Ungerstedt U (1986) An in vivo study of dopamine release and metabolism in rat brain regions using intracerebral dialysis. J Neurochem (in press)
Shults CW, Yajima H, Gullner H-G, Chase TN, O'Donohue TL (1985) Demonstration and distribution of kassinin-like material (substance K) in the rat central nervous system. J Neurochem 45: 552–558
Somogyi P, Bolam JP, Tottendell S, Smith AD (1981) Monosynaptic input from the nucleus accumbens-ventral striatum region to retrogradely labelled nigrostriatal neurones. Brain Res 217: 245–263
Somogyi P, Priestly JV, Cuello AC, Smith AD, Bolam JP (1982) Synaptic connection of substance P-immunoreactive nerve terminals in the substantia nigra of the rat. Cell Tissue Res 223: 469–486
Starr MS, James TA, Gaytten D (1978) Behavioural depressant and antinociceptive properties of substance P in the mouse: possible implication of brain monoamines. Eur J Pharmacol 48: 203–212
Starr MS, Summerhayes M, Kilpatrick IC (1983) Interactions between dopamine and gamma-aminobutyrate in the substantia nigra: implications for the striatonigral output hypothesis. Neuroscience 8: 547–559
Sutor B, Zieglgänsberger W (1984) Actions of D-Ala2-D-Leu5-Enkephalin and Dynorphin A (1–17) on neocortical neurons in vitro. Neuropeptides 5: 241–244
Tachibana S, Araki I, Ohya S, Hoshida S (1982) Isolation and structure of dynorphin, an opioid peptide, from porcine duodenum. Nature 295: 339–340
Torrens Y, Beaujouan JC, Besson MJ, Michelot R, Glowinski J (1981) Inhibitory effects of GABA, L-glutamic acid and nicotine on the potassium-evoked release of substance P in substantia nigra slices of the rat. Eur J Pharmacol 71: 383–392
Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 24: 485–493
Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367: 69–93
Ungerstedt U, Herrera-Marschitz M (1981) Behavioural pharmacology of dopamine receptor mechanisms. In: Stjärne L, Hedqvist P, Lagercrantz H, Wennmalm Å (eds) Chemical neurotransmission: 75 years. Academic Press, New York, pp 481–494
Ungerstedt U (1984) Measurement of neurotransmitter release by intracranial dialysis. In: Marsden CA (ed) Measurement of neurotransmitter release in vivo. J Wiley & Sons Ltd, Chichester, pp 81–105
Van den Pol AN, Smith AD, Powell JF (1985) GABA axons in synaptic contact with dopamine neurons in the double immunocytochemistry with biotin-peroxidase and protein Acolloidal gold. Brain Res 348: 146–154
Vidal C, Maier R, Zieglgänsberger W (1985) Effects of dynorphin A (1–17), dynorphin A (1–13) and D-Ala2-D-Leu5-enkephalin on the excitability of pyramidal cells in CA1 and CA2 of the rat hippocampus in vitro. Neuropeptides 5: 237–240
Vincent SR, Hattori T, McGeer EG (1978) The nigro-tectal projection: a biochemical and ultrastructural characterization. Brain Res 151: 159–164
Vincent SR, Hökfelt T, Christensson I, Terenius L (1982a) Dynorphin-immunoreactive neurons in the central nervous system. Neurosci Lett 33: 185–190
Vincent SR, Hökfelt T, Christensson I, Terenius L (1982b) Immunohistochemical evidence for a dynorphin immunoreactive striato-nigral pathway. Eur J Pharmacol 85: 251–252
Von Voigtlander PF, Lahti RA, Ludens JH (1983) U-50, 488: a selective and structurally novel non-Mu (Kappa) opioid agonist. J Pharmacol Exp Ther 224: 7–12
Waldmeier PC, Kam R, Stöcklin K (1978) Increased dopamine metabolism in rat striatum after infusions of substance P into the substantia nigra. Brain Res 159: 223–227
Walker RJ, Kemp JA, Yajima H, Kitagawa K, Woodruff GN (1976) The action of substance P on mesencephalic reticular and substantia nigral neurones of the rat. Experentia 32: 214–215
Walker JM, Moises HC, Coy DH, Akil GBH (1982a) Nonopiate effects of dynorphin and Des-Tyr-dynorphin. Science 218: 1136–1138
Walker JM, Moises HC, Coy DH, Baldright G, Akil GBH (1982b) Comparison of the distribution of dynorphin systems and enkephalin systems in brain. Science 218: 1134–1138
Wassef M, Berod A, Sotelo C (1981) Dopaminergic dendrites in the pars reticulata of the rat substantia nigra and their striatal input. Combined immunocytochemical localization of tyrosine hydroxylase and anterograde degeneration. Neuroscience 6: 2125–2139
Weber E, Roth KA, Barchas JD (1982) Immunohistochemical distribution of α-neo-endorphin/dynorphin neuronal systems in rat brain: evidence for colocalization. Proc Natl Acad Sci USA 79: 3062–3066
Werz MA, MacDonald RL (1984) Dynorphin reduces calcium-dependent action potential duration by decreasing voltage-dependent calcium conductance. Neurosci Lett 46: 185–190
Westerink BHC (1985) Commentary: sequence and significance of dopamine metabolism in the rat brain. Neurochem Int 7: 221–227
Williams J, Davies JA (1983) The involvement of 5-HT in the release of dendritic dopamine from slices of rat substantia nigra. J Pharm Pharmacol 35: 734–737
William MN, Faull RLM (1985) The striatonigral projection and nigrotectal neurons in the rat. A correlated light and electron microscopic study demonstrating a monosynaptic striatal input to identified nigrotectal neurons using a combined degeneration and horseradish peroxidase procedure. Neuroscience 14: 991–1010
Zamir N, Palkovits M, Brownstein MJ (1983) Distribution of immunoreactive dynorphin in the central nervous system of the rat. Brain Res 280: 81–93
Zamir N, Palkovits M, Brownstein MJ (1984a) Distribution of immunoreactive dynorphin A1–8 in discrete nuclei of the rat brain: comparison with dynorphin A. Brain Res 307: 61–68
Zamir N, Palkovits M, Weber E, Mezey E, Brownstein MJ (1984b) A dynorphinergic pathway of leu-enkephalin production in substantia nigra. Nature 307: 643–645
Zamir N, Palkovits M, Brownstein MJ (1984c) Distribution of immunoreactive β-neoendorphin in discrete areas of the rat brain and pituitary gland: comparison with α-neoendorphin. Neurosci 4: 1248–1252
Zamir N, Palkovits M, Brownstein MJ (1984d) The distribution of immunoreactive α-neoendorphin in the central nervous system of the rat. J Neurosci 4: 1240–1247
Zamir N, Palkovits M, Weber E, Brownstein MJ (1984e) Distribution of immunoreactive dynorphin B in discrete areas of the rat brain and spinal cord. Brain Res 300: 121–127
Zetterström T, Sharp T, Marsden CA, Ungerstedt U (1983) In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J Neurochem 41: 1769–1773
Zetterström T, Sharp T, Ungerstedt U (1984) Effect of neuroleptic drugs on striatal dopamine release and metabolism in the awake rat studied by intracerebral dialysis. Eur J Pharmacol 106: 27–37
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Herrera-Marschitz, M., Christensson-Nylander, I., Sharp, T. et al. Striato-nigral dynorphin and substance P pathways in the rat. Exp Brain Res 64, 193–207 (1986). https://doi.org/10.1007/BF00238214
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DOI: https://doi.org/10.1007/BF00238214