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Intrastriatal injection of dl-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine

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Abstract

dl-2-amino-5-phosphonovaleric acid (AP-5), which blocks glutamatergic transmission at the NMDA-preferring receptor, was injected into the antero-dorsal striatum of rats. AP-5-induced behavioural changes were assessed i) using a stereotypy rating scale and ii) using an experimental chamber designed to quantify sniffing. In both behavioural situations it was shown that AP-5 (10 μg/0.5 μl) induced continuous intensive sniffing similar to that induced by small doses of systemically administered amphetamine or apomorphine. However, oral stereotypies were not induced by AP-5. Systemically injected clozapine (5 and 10 mg/kg SC) as well as haloperidol (0.1 mg/kg IP) antagonized AP-5-induced sniffing. These results show that besides dopamine receptors, NMDA receptors are involved in the control of sniffing. In behavioural terms, the effect of glutamate mediated by the NMDA receptor in the striatum is opposite to that of dopamine.

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References

  • Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35:53–68

    Google Scholar 

  • Björklund A, Lindvall O (1984) Dopamine-containing systems in the CNS. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 2, part I. Elsevier Science, Amsterdam, pp 55–122

    Google Scholar 

  • Bürki HR, Eichenberger E, Sayers AC, White TG (1975) Clozapine and the dopamine hypothesis of schizophrenia, a critical appraisal. Pharmacopsychiatry 8:115–121

    Google Scholar 

  • Carter CJ (1980) Glutamatergic pathways from medial prefrontal cortex to the anterior striatum, nucleus accumbens and substantia nigra. Br J Pharmacol 72: 50

    Google Scholar 

  • Davies J, Evans RH, Jones AW, Mewett KN, Smith DAS, Watkins JC (1983) Recent advances in the pharmacology of excitatory amino acids in the mammilian central nervous system. In: Fuxe K, Roberts P, Schwarcz R (eds) Wenner-Gren Int Symp, vol 39. Macmillan Press, London, pp 43–54

    Google Scholar 

  • Divac I, Öberg RGE (1979) The neostriatum. Pergamon Press, Oxford New York Toronto

    Google Scholar 

  • Donzanti BA, Uretsky NJ (1984) Antagonism of the hypermotility response induced by excitatory amino acids in the rat nucleus accumbens. Naunyn-Schmiedeberg's Arch Pharmacol 325:1–7

    Google Scholar 

  • Fonnum F (1984) Glutamate: A neurotransmitter in mammalian brain. J Neurochem 42:1–11

    Google Scholar 

  • Fray PJ, Sahakian BJ, Robbins TW, Koob GF, Iversen SD (1980) An observational method for quantifying the behavioural effects of dopamine agonists: contrasting effects of d-amphetamine and apomorphine. Psychopharmacology 69:253–259

    Google Scholar 

  • Godukhin OV, Zharikova AD, Novoselov VI (1980) The release of labeled l-glutamic acid from rat neostriatum in vivo following stimulation of frontal cortex. Neuroscience 5:2151–2154

    Google Scholar 

  • Hassler R, Haug P, Nitsch C, Kim JS, Paik K (1982) Effect of motor and premotor cortex ablation on concentrations of amino acids, monoamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter. J Neurochem 38:1087–1098

    Google Scholar 

  • Havemann U, Turski L, Schwarz M, Kuschinsky K (1983) Nigral GABA ergic mechanisms and EMG activity in rats: Differences between pars reticulata and pars compacta. Eur J Pharmacol 92:49–56

    Google Scholar 

  • Herrling PL (1985) Pharmacology of the cortico-caudate EPSP in the cat: Evidence for its mediation by quisqualate- or kainate-receptors. Neuroscience 14:417–426

    Google Scholar 

  • Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522

    Google Scholar 

  • Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 20:379–382

    Google Scholar 

  • Kornhuber HH (1983) Chemistry, physiology and neuropsychology of schizophrenia: Towards an earlier diagnosis of schizophrenia I. Archiv Psychiatr Nervenkr 233:415–422

    Google Scholar 

  • Lehmann J, Scatton B (1982) Characterization of the excitatory amino acid receptor-mediated release of [3H]acetylcholine from rat striatal slices. Brain Res 252:77–89

    Google Scholar 

  • Lehmann J, Schaefer P, Ferkany JW, Coyle JT (1983) Quinolinic acid evokes [3H]acetylcholine release in striatal slices: mediation by NMDA-type excitatory amino acid receptors. Eur J Pharmacol 96:111–115

    Google Scholar 

  • Lienert GA (1973) Verteilungsfreie Methoden in der Biostatistik, part I. Anton Hain, Meisenheim

    Google Scholar 

  • Ljungberg T, Ungerstedt U (1978) Classification of neuroleptic drugs according to their ability to inhibit apomorphine-induced locomotion and gnawing: Evidence for two different mechanisms of action. Psychopharmacology 56:239–247

    Google Scholar 

  • Meldrum BS, Chapman AG (1983) Excitatory amino acids and anticonvulsant drug action. Glutamine, glutamate, and GABA in the central nervous system. Alan R. Liss Press, New York, pp 625–641

    Google Scholar 

  • Monoghan DT, Cotman CW (1985) Distribution of N-methyl-D-aspartate-sensitive l-[3H]glutamate-binding sites in rat brain. J Neurosci 11:2909–2919

    Google Scholar 

  • Nieoullon A, Kerkerian L, Dusticier N (1983) Presynaptic dopaminergic control of high affinity glutamate uptake in the striatum. Neurosci Lett 43:191–196

    Google Scholar 

  • Olverman HJ, Jones AW, Watkins JC (1984) l-Glutamate has higher affinity than other amino acids for [3H]-d-AP-5 binding sites in rat brain membranes. Nature 307:460–462

    Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, Sydney New York London

    Google Scholar 

  • Pycock CJ, Kerwin RW, Carter CJ (1980) Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats. Nature 286:74–77

    Google Scholar 

  • Rebec GV, Bashore TR (1984) Critical issues in assessing the behavioral effects of amphetamine. Neurosci Biobehav Rev 8:153–159

    Google Scholar 

  • Robertson A, MacDonald C (1984) Atypical neuroleptics clozapine and thioridazine enhance amphetamine-induced stereotypy. Pharmacol Biochem Behav 21:97–101

    Google Scholar 

  • Rowlands GJ, Roberts PJ (1980a) Activation of dopamine receptors inhibits calcium-dependent glutamate release from corticostriatal terminals in vitro. Eur J Pharmacol 62:241–242

    Google Scholar 

  • Rowlands GJ, Roberts PJ (1980b) Specific calcium-dependent release of endogenous glutamate from rat striatum is reduced by destruction of the cortico-striatal tract. Exp Brain Res 39:239–240

    Google Scholar 

  • Sandberg M, Ward HK, Bradford HF (1985) Effect of corticostriate pathway lesion on the activities of enzymes involved in synthesis and metabolism of amino acid neurotransmitters in the striatum. J Neurochem 44:42–47

    Google Scholar 

  • Scatton B, Lehmann J (1982) N-methyl-d-aspartate-type receptors mediate striatal 3H-acetylcholine release evoked by excitatory amino acids. Nature 297:422–424

    Google Scholar 

  • Scatton B, Worms P, Lloyd KG, Bartholini G (1982) Cortical modulation of striatal function. Brain Res 232:331–343

    Google Scholar 

  • Schmidt WJ (1985a) Striatal glutamic acid and behaviour. Neurosci Lett (Suppl 22):93

  • Schmidt WJ (1985b) Glutamate antagonists induce stereotyped behaviour. Pharmacopsychiatry (in press)

  • Schmidt WJ (1986) Striatal glutamic acid and the behaviour of the rat. Verh Dtsch Zool Ges (in press)

  • Sladeczek F, Pin JP, Recasens M, Bockaert J, Weiss S (1985) Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 317:717–719

    Google Scholar 

  • Spencer H (1976) Antagonism of cortical excitation of striatal neurones by glutamate as an excitatory transmitter in the rat striatum. Brain Res 102:91–101

    Google Scholar 

  • Stone TW (1979) Amino acids as neurotransmitters of corticofugal neurones in the rat: A comparison of glutamate and aspartate. Br J Pharmacol 67:545–551

    Google Scholar 

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Schmidt, W.J. Intrastriatal injection of dl-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine. Psychopharmacology 90, 123–130 (1986). https://doi.org/10.1007/BF00172883

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  • DOI: https://doi.org/10.1007/BF00172883

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