Skip to main content
NCBI home page
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 2005 Apr;25(2):371–392. doi: 10.1007/s10571-005-3065-8

Role of Nitric Oxide on Motor Behavior

E A Del Bel 1,5,✉, F S Guimarães 2, M Bermũdez-Echeverry 1, M Z Gomes 1,3, A Schiaveto-de-Souza 1, F E Padovan-Neto 1, V Tumas 1, A P Barion-Cavalcanti 1,4, M Lazzarini 1,4, L P Nucci-da-Silva 1, D de Paula-Souza1 1
PMCID: PMC11529539  PMID: 16047547

Abstract

The present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena.

These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), NG-nitro-L-arginine methylester (L-NAME), NG-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration.

Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfa1 adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice.

L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta.

Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the cataleptic effect of haloperidol, raising the possibility that such treatments could decrease motor side effects associated with antipsychotic medications.

Finally, recent studies using experimental Parkinson’s disease models suggest an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. It provides evidence of a protective role of NO. Together, our results indicate that NO may be a key participant on physiological and pathophysiological processes in the nigrostriatal system.

Keywords: catalepsy, L-NOARG, 7-NIO, nitric oxide synthase, L-arginine, haloperidol, tolerance, dopamine, NADPH-diaphorase, intracerebral injection, anxiogenic, anxiolytic, Parkinson

References

  1. Abekawa, T., Ohmori, T., and Koyama, T. (1994). Effect of NO synthase inhibition on behavioral changes induced by a single administration of methamphetamine. Brain Res.666:147–150. [DOI] [PubMed] [Google Scholar]
  2. Agid, Y., Javoy-Agid, F., and Ruberg, M. (1987). Biochemistry of neurotransmitters in Parkinson’s disease. In Marsden, C. D., and Fahn, S. (eds.), Movement Disorders, Butterworths, London, pp. 166–230. [Google Scholar]
  3. Allikmets, L. H., Zarkovsky, A. M., and Nurk, A. M. (1981). Changes in catalepsy and receptor sensitivity following chronic neuroleptic treatment. Eur. J. Pharmacol.75:145–147. [DOI] [PubMed] [Google Scholar]
  4. Amalric, M., Moukhles, H., Nieoullon, A., and Daszuta, A. (1995). Complex deficits on reaction time performance following bilateral intrastriatal 6-OHDA infusion in the rat. Eur. J. Neurosci.7:972–980. [DOI] [PubMed] [Google Scholar]
  5. Araki, T., Mizutani, H., Matsubara, M., Imai, Y., Mizugaki, M., and Itoyama, Y. (2001). Nitric oxide synthase inhibitors cause motor deficits in mice. Eur. Neuropsychopharmacol.11:125–133. [DOI] [PubMed] [Google Scholar]
  6. Ariano, M. A. (1983). Distribution of components of the guanosine 3′,5′-phosphate system in rat caudate-putamen. Neuroscience10:707–723. [DOI] [PubMed] [Google Scholar]
  7. Ariano, M. A., Lewicki, J. A., Brandwein, H. J., and Murad, F. (1982). Immunohistochemical localization of guanylate cyclase within neurons of rat brain. Proc. Natl. Acad. Sci. U.S.A79:1316–1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ariano, M. A., and Matus, A. I. (1981). Ultrastructural localization of cyclic GMP and cyclic AMP in rat striatum. J. Cell Biol.91:287–292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Babbedge, R. C., Hart, S. L., and Moore, P. K. (1993a). Anti-nociceptive activity of nitric oxide synthase inhibitors in the mouse: Dissociation between the effect of L-NAME and L-NMMA. J. Pharm. Pharmacol.45:77–79. [DOI] [PubMed] [Google Scholar]
  10. Babbedge, R. C., Wallace, P., Gaffen, Z. A., Hart, S. L., and Moore, P. K. (1993b). L-NG-nitro arginine p-nitroanilide (L-NAPNA) is anti-nociceptive in the mouse. Neuroreport4:307–310. [DOI] [PubMed] [Google Scholar]
  11. Barjavel, M. J., and Bhargava, H. N. (1995). Nitric oxide synthase activity in brain regions and spinal cord of mice and rats: Kinetic analysis. Pharmacology50:168–174. [DOI] [PubMed] [Google Scholar]
  12. Barneoud, P., Parmentier, S., Mazadier, M., Miquet, J. M., Boireau, A., Dubedat, P., and Blanchard, J. C. (1995). Effects of complete and partial lesions of the dopaminergic mesotelencephalic system on skilled forelimb use in the rat. Neuroscience67:837–848. [DOI] [PubMed] [Google Scholar]
  13. Black, M. D., Matthews, E. K., and Humphrey, P. P. (1994). The effects of a photosensitive nitric oxide donor on basal and electrically-stimulated dopamine efflux from the rat striatum in vitro. Neuropharmacology33:1357–1365. [DOI] [PubMed] [Google Scholar]
  14. Bohme, G. A., Bon, C., Stutzmann, J. M., Doble, A., and Blanchard, J. C. (1991). Possible involvement of nitric oxide in long-term potentiation. Eur. J. Pharmacol.199:379–381. [DOI] [PubMed] [Google Scholar]
  15. Bredt, D. S. (1999). Endogenous nitric oxide synthesis: Biological functions and pathophysiology. Free Radic. Res.31:577–596. [DOI] [PubMed] [Google Scholar]
  16. Bredt, D. S., Hwang, P. M., and Snyder, S. H. (1990). Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature347:768–770. [DOI] [PubMed] [Google Scholar]
  17. Bredt, D. S., and Snyder, S. H. (1990). Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. U.S.A87:682–685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Bredt, D. S., and Snyder, S. H. (1992). Nitric oxide, a novel neuronal messenger. Neuron8:3–11. [DOI] [PubMed] [Google Scholar]
  19. Buisson, A., Margaill, I., Callebert, J., Plotkine, M., and Boulu, R. G. (1993). Mechanisms involved in the neuroprotective activity of a nitric oxide synthase inhibitor during focal cerebral ischemia. J. Neurochem.61:690–696. [DOI] [PubMed] [Google Scholar]
  20. Calabresi, P., Pisani, A., Centonze, D., and Bernardi, G. (1997). Synaptic plasticity and physiological interactions between dopamine and glutamate in the striatum. Neurosci. Biobehav. Rev.21:519–523. [DOI] [PubMed] [Google Scholar]
  21. Carreau, A., Duval, D., Poignet, H., Scatton, B., Vige, X., and Nowicki, J. P. (1994). Neuroprotective efficacy of N omega-nitro-L-arginine after focal cerebral ischemia in the mouse and inhibition of cortical nitric oxide synthase. Eur. J. Pharmacol.256:241–249. [DOI] [PubMed] [Google Scholar]
  22. Castagnoli, K., Palmer, S., and Castagnoli, N., Jr. (1999). Neuroprotection by (R)-deprenyl and 7-nitroindazole in the MPTP C57BL/6 mouse model of neurotoxicity. Neurobiology (Bp)7:135–149. [PubMed] [Google Scholar]
  23. Caton, P. W., Tousman, S. A., and Quock, R. M. (1994). Involvement of nitric oxide in nitrous oxide anxiolysis in the elevated plus-maze. Pharmacol. Biochem. Behav.48:689–692. [DOI] [PubMed] [Google Scholar]
  24. Cavas, M., and Navarro, J. F. (2002). Coadministration of L-NOARG and tiapride: Effects on catalepsy in male mice. Prog. Neuropsychopharmacol. Biol. Psychiatry26:69–73. [DOI] [PubMed] [Google Scholar]
  25. Cheramy, A., Leviel, V., and Glowinski, J. (1981). Dendritic release of dopamine in the substantia nigra. Nature289:537–542. [DOI] [PubMed] [Google Scholar]
  26. Choi, D. W. (1993). Nitric oxide: Foe or friend to the injured brain? Proc. Natl. Acad. Sci. U.S.A.90:9741–9743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Clarke, K. A., and Still, J. (1999). Gait analysis in the mouse. Physiol. Behav.66:723–729. [DOI] [PubMed] [Google Scholar]
  28. Coderre, T. J. (1993). The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats. Mol. Neurobiol.7:229–246. [DOI] [PubMed] [Google Scholar]
  29. Cohen, G. (1987). Monoamine oxidase, hydrogen peroxide, and Parkinson’s disease. Adv. Neurol.45:119–125. [PubMed] [Google Scholar]
  30. Contestabile, A. (2000). Roles of NMDA receptor activity and nitric oxide production in brain development. Brain Res. Brain Res. Rev.32:476–509. [DOI] [PubMed] [Google Scholar]
  31. Costall, B., Marsden, C. D., Naylor, R. J., and Pycock, C. J. (1976). The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain. Brain Res.118:87–113. [DOI] [PubMed] [Google Scholar]
  32. Costall, B., and Naylor, R. J. (1975). A comparison of circling models for the detection of antiparkinson activity. Psychopharmacologia41:57–64. [DOI] [PubMed] [Google Scholar]
  33. Dall’Igna, O. P., Dietrich, M. O., Hoffmann, A., Neto, W., Vendite, D., Souza, D. O., and Lara, D. R. (2001). Catalepsy and hypolocomotion induced by a nitric oxide donor: Attenuation by theophylline. Eur. J. Pharmacol.432:29–33. [DOI] [PubMed] [Google Scholar]
  34. Danysz, W., Gossel, M., Zajaczkowski, W., Dill, D., and Quack, G. (1994). Are NMDA antagonistic properties relevant for antiparkinsonian-like activity in rats?—Case of amantadine and memantine. J. Neural Transm. Park Dis. Dement. Sect.7:155–166. [DOI] [PubMed] [Google Scholar]
  35. Dawson, T. M., Bredt, D. S., Fotuhi, M., Hwang, P. M., and Snyder, S. H. (1991). Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc. Natl. Acad. Sci. U.S.A.88:7797–7801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. de Medinaceli, L., Freed, W. J., and Wyatt, R. J. (1982). An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp. Neurol.77:634–643. [DOI] [PubMed] [Google Scholar]
  37. De Oliveira, C. L., Del Bel, E. A., and Guimaraes, F. S. (1997a). Effects of L-NOARG on plus-maze performance in rats. Pharmacol. Biochem. Behav.56:55–59. [DOI] [PubMed] [Google Scholar]
  38. De Oliveira, C. L., Del Bel, E. A., and Guimaraes, F. S. (1997b). Effects of L-NOARG on plus-maze performance in rats. Pharmacol. Biochem. Behav.56:55–59. [DOI] [PubMed] [Google Scholar]
  39. De Oliveira, R. M., Del Bel, E. A., and Guimaraes, F. S. (2001). Effects of excitatory amino acids and nitric oxide on flight behavior elicited from the dorsolateral periaqueductal gray. Neurosci. Biobehav. Rev.25:679–685. [DOI] [PubMed] [Google Scholar]
  40. Del Bel, E. A., da Silva, C. A., and Guimaraes, F. S. (1998). Catalepsy induced by nitric oxide synthase inhibitors. Gen. Pharmacol.30:245–248. [DOI] [PubMed] [Google Scholar]
  41. Del Bel, E. A., da Silva, C. A., Guimaraes, F. S., and Bermudez-Echeverry, M. (2004). Catalepsy induced by intra-striatal administration of nitric oxide synthase inhibitors in rats. Eur. J. Pharmacol.485:175–181. [DOI] [PubMed] [Google Scholar]
  42. Del Bel, E. A., and Guimaraes, F. S. (2000). Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice. Psychopharmacology (Berl)147:356–361. [DOI] [PubMed] [Google Scholar]
  43. Del Bel, E. A., Oliveira, P. R., Oliveira, J. A., Mishra, P. K., Jobe, P. C., and Garcia-Cairasco, N. (1997). Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models. Braz. J. Med. Biol. Res.30:971–979. [DOI] [PubMed] [Google Scholar]
  44. Del Bel, E. A., Souza, A. S., Guimaraes, F. S., da Silva, C. A., and Nucci-da-Silva, L. P. (2002). Motor effects of acute and chronic inhibition of nitric oxide synthesis in mice. Psychopharmacology (Berl)161:32–37. [DOI] [PubMed] [Google Scholar]
  45. Deumens, R., Blokland, A., and Prickaerts, J. (2002). Modeling Parkinson’s disease in rats: An evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp. Neurol.175:303–317. [DOI] [PubMed] [Google Scholar]
  46. Dwyer, M. A., Bredt, D. S., and Snyder, S. H. (1991). Nitric oxide synthase: Irreversible inhibition by L-NG-nitroarginine in brain in vitro and in vivo. Biochem. Biophys. Res. Commun.176:1136–1141. [DOI] [PubMed] [Google Scholar]
  47. Dzoljic, E., De Vries, R., and Dzoljic, M. R. (1997). New and potent inhibitors of nitric oxide synthase reduce motor activity in mice. Behav. Brain Res.87:209–212. [DOI] [PubMed] [Google Scholar]
  48. Elliott, P. J., Close, S. P., Walsh, D. M., Hayes, A. G., and Marriott, A. S. (1990). Neuroleptic-induced catalepsy as a model of Parkinson’s disease. I. Effect of dopaminergic agents. J. Neural Transm. Park Dis. Dement. Sect.2:79–89. [DOI] [PubMed] [Google Scholar]
  49. Esplugues, J. V. (2002). NO as a signalling molecule in the nervous system. Br. J. Pharmacol.135:1079–1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Eve, D. J., Nisbet, A. P., Kingsbury, A. E., Hewson, E. L., Daniel, S. E., Lees, A. J., Marsden, C. D., and Foster, O. J. (1998). Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson’s disease. Brain Res. Mol. Brain Res.63:62–71. [DOI] [PubMed] [Google Scholar]
  51. Ezrin-Waters, C., and Seeman, P. (1977). Tolerance of haloperidol catalepsy. Eur. J. Pharmacol.41:321–327. [DOI] [PubMed] [Google Scholar]
  52. Fahn, S. (1988). Parkinsonism. In Wyngaarden, J. B., and Smith, L. H., Jr. (eds.), Cecil’s Textbook of medicine, Saunders, Philadelphia, pp. 2143–2147. [Google Scholar]
  53. Faria, M. S., Muscara, M. N., Moreno, J. H., Teixeira, S. A., Dias, H. B., De Oliveira, B., Graeff, F. G., and De Nucci, G. (1997). Acute inhibition of nitric oxide synthesis induces anxiolysis in the plus maze test. Eur. J. Pharmacol.323:37–43. [DOI] [PubMed] [Google Scholar]
  54. Forstermann, U., Schmidt, H. H., Pollock, J. S., Sheng, H., Mitchell, J. A., Warner, T. D., Nakane, M., and Murad, F. (1991). Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem. Pharmacol.42:1849–1857. [DOI] [PubMed] [Google Scholar]
  55. Garthwaite, J. (1991). Glutamate, nitric oxide and cell–cell signalling in the nervous system. Trends Neurosci.14:60–67. [DOI] [PubMed] [Google Scholar]
  56. Gerlach, M., and Riederer, P. (1996). Animal models of Parkinson’s disease: An empirical comparison with the phenomenology of the disease in man. J. Neural Trans.103:987–1041. [DOI] [PubMed] [Google Scholar]
  57. Goldberger, M. E., Bregman, B. S., Vierck, C. J., Jr., and Brown, M. (1990). Criteria for assessing recovery of function after spinal cord injury: Behavioral methods. Exp. Neurol.107:113–117. [DOI] [PubMed] [Google Scholar]
  58. Gomes, M. Z., and Del Bel, E. A. (2003). Effects of electrolytic and 6-hydroxydopamine lesions of rat nigrostriatal pathway on nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase. Brain Res. Bull.62:107–115. [DOI] [PubMed] [Google Scholar]
  59. Graeff, F. G. (1990). Brain defense system and anxiety. In Burrows, G. D., Roth, M., and Noyes, R. (eds.), Handbook of Anxiety, Elsevier Science, Amsterdam, pp. 307–354. [Google Scholar]
  60. Graveland, G. A., Williams, R. S., and DiFiglia, M. (1985). Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington’s disease. Science227:770–773. [DOI] [PubMed] [Google Scholar]
  61. Graybiel, A. M. (1990). Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci.13:244–254. [DOI] [PubMed] [Google Scholar]
  62. Graybiel, A. M., Besson, M. J., and Weber, E. (1989). Neuroleptic-sensitive binding sites in the nigrostriatal system: Evidence for differential distribution of sigma sites in the substantia nigra, pars compacta of the cat. J. Neurosci.9:326–338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Greenberg, J. H., Hamada, J., and Rysman, K. (1997). Distribution of N(omega)-nitro-L-arginine following topical and intracerebroventricular administration in the rat. Neurosci. Lett.229:1–4. [DOI] [PubMed] [Google Scholar]
  64. Guevara-Guzman, R., Emson, P. C., and Kendrick, K. M. (1994). Modulation of in vivo striatal transmitter release by nitric oxide and cyclic GMP. J. Neurochem.62:807–810. [DOI] [PubMed] [Google Scholar]
  65. Guimaraes, F. S., de Aguiar, J. C., Del Bel, E. A., and Ballejo, G. (1994). Anxiolytic effect of nitric oxide synthase inhibitors microinjected into the dorsal central grey. Neuroreport5:1929–1932. [DOI] [PubMed] [Google Scholar]
  66. Hantraye, P., Brouillet, E., Ferrante, R., Palfi, S., Dolan, R., Matthews, R. T., and Beal, M. F. (1996). Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nat. Med.2:1017–1021. [DOI] [PubMed] [Google Scholar]
  67. Hauber, W. (1998). Involvement of basal ganglia transmitter systems in movement initiation. Prog. Neurobiol.56:507–540. [DOI] [PubMed] [Google Scholar]
  68. Hecker, M., Mitchell, J. A., Harris, H. J., Katsura, M., Thiemermann, C., and Vane, J. R. (1990). Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine. Biochem. Biophys. Res. Commun.167:1037–1043. [DOI] [PubMed] [Google Scholar]
  69. Hirsch, E. C., Graybiel, A. M., Duyckaerts, C., and Javoy-Agid, F. (1987). Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc. Natl. Acad. Sci. U.S.A.84:5976–5980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Hope, B. T., Michael, G. J., Knigge, K. M., and Vincent, S. R. (1991). Neuronal NADPH diaphorase is a nitric oxide synthase. Proc. Natl. Acad. Sci. U.S.A88:2811–2814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Hoyt, K. R., Tang, L. H., Aizenman, E., and Reynolds, I. J. (1992). Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons. Brain Res.592:310–316. [DOI] [PubMed] [Google Scholar]
  72. Hughes, R. N. (1993). Effects on open-field behavior of diazepam and buspirone alone and in combination with chronic caffeine. Life Sci.53:1217–1225. [DOI] [PubMed] [Google Scholar]
  73. Hunot, S., Boissiere, F., Faucheux, B., Brugg, B., Mouatt-Prigent, A., Agid, Y., and Hirsch, E. C. (1996). Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience72:355–363. [DOI] [PubMed] [Google Scholar]
  74. Iadecola, C., Xu, X., Zhang, F., Hu, J., and el Fakahany, E. E. (1994). Prolonged inhibition of brain nitric oxide synthase by short-term systemic administration of nitro-L-arginine methyl ester. Neurochem. Res.19:501–505. [DOI] [PubMed] [Google Scholar]
  75. Inglis, W. L., and Winn, P. (1995). The pedunculopontine tegmental nucleus: Where the striatum meets the reticular formation. Prog. Neurobiol.47:1–29. [DOI] [PubMed] [Google Scholar]
  76. Iravani, M. M., Millar, J., and Kruk, Z. L. (1998). Differential release of dopamine by nitric oxide in subregions of rat caudate putamen slices. J. Neurochem.71:1969–1977. [DOI] [PubMed] [Google Scholar]
  77. Iversen, S. D., Howells, R. B., and Hughes, R. P. (1980). Behavioral consequences of long-term treatment with neuroleptic drugs. Adv. Biochem. Psychopharmacol.24:305–313. [PubMed] [Google Scholar]
  78. Iwamoto, E. T., Loh, H. H., and Way, E. L. (1976). Circling behavior in rats with 6-hydroxydopamine or electrolytic nigral lesions. Eur. J. Pharmacol.37:339–356. [DOI] [PubMed] [Google Scholar]
  79. Johnsson, G. (1983). Chemical lesioning techniques:monoamine neurotoxins. In Bjorklund, A., and Hokfelt, T. (eds.), Handbook of Chemical Neuroanatomy, Sciences Publishers, Amsterdam, pp. 463–507. [Google Scholar]
  80. Johnston, H. M., and Morris, B. J. (1994). NMDA and nitric oxide increase microtubule-associated protein 2 gene expression in hippocampal granule cells. J. Neurochem.63:379–382. [DOI] [PubMed] [Google Scholar]
  81. Kawaguchi, Y. (1993). Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum. J. Neurosci.13:4908–4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Keifer, J., and Kalil, K. (1991). Effects of infant versus adult pyramidal tract lesions on locomotor behavior in hamsters. Exp. Neurol.111:98–105. [DOI] [PubMed] [Google Scholar]
  83. Kiss, J. P., and Vizi, E. S. (2001). Nitric oxide: A novel link between synaptic and nonsynaptic transmission. Trends Neurosci.24:211–215. [DOI] [PubMed] [Google Scholar]
  84. Klatt, P., Heinzel, B., John, M., Kastner, M., Bohme, E., and Mayer, B. (1992). Ca2+/calmodulin-dependent cytochrome c reductase activity of brain nitric oxide synthase. J. Biol. Chem.267:11374–11378. [PubMed] [Google Scholar]
  85. Klemm, W. R. (1983). Cholinergic-dopaminergic interactions in experimental catalepsy. Psychopharmacology (Berl)81:24–27. [DOI] [PubMed] [Google Scholar]
  86. Klemm, W. R. (1985). Evidence for a cholinergic role in haloperidol-induced catalepsy. Psychopharmacology (Berl)85:139–142. [DOI] [PubMed] [Google Scholar]
  87. Koffer, K. B., Berney, S., and Hornykiewicz, O. (1978). The role of the corpus striatum in neuroleptic- and narcotic-induced catalepsy. Eur. J. Pharmacol.47:81–86. [DOI] [PubMed] [Google Scholar]
  88. Kolesnikov, Y. A., Pick, C. G., and Pasternak, G. W. (1992). NG-nitro-L-arginine prevents morphine tolerance. Eur. J. Pharmacol.221:399–400. [DOI] [PubMed] [Google Scholar]
  89. Koob, G. F., Simon, H., Herman, J. P., and Le Moal, M. (1984). Neuroleptic-like disruption of the conditioned avoidance response requires destruction of both the mesolimbic and nigrostriatal dopamine systems. Brain Res.303:319–329. [DOI] [PubMed] [Google Scholar]
  90. Korf, J., and Sebens, J. B. (1987). Relationship between dopamine receptor occupation by spiperone and acetylcholine levels in the rat striatum after long-term haloperidol treatment depends on dopamine innervation. J. Neurochem.48:516–521. [DOI] [PubMed] [Google Scholar]
  91. Kriegsfeld, L. J., Eliasson, M. J., Demas, G. E., Blackshaw, S., Dawson, T. M., Nelson, R. J., and Snyder, S. H. (1999). Nocturnal motor coordination deficits in neuronal nitric oxide synthase knock-out mice. Neuroscience89:311–315. [DOI] [PubMed] [Google Scholar]
  92. Kulig, B. M., Vanwersch, R. A., and Wolthuis, O. L. (1985). The automated analysis of coordinated hindlimb movement in rats during acute and prolonged exposure to toxic agents. Toxicol. Appl. Pharmacol.80:1–10. [DOI] [PubMed] [Google Scholar]
  93. Kunkel-Bagden, E., Dai, H. N., and Bregman, B. S. (1993). Methods to assess the development and recovery of locomotor function after spinal cord injury in rats. Exp. Neurol.119:153–164. [DOI] [PubMed] [Google Scholar]
  94. Lavoie, B., and Parent, A. (1994). Pedunculopontine nucleus in the squirrel monkey: Projections to the basal ganglia as revealed by anterograde tract-tracing methods. J. Comp Neurol.344:210–231. [DOI] [PubMed] [Google Scholar]
  95. Linden, D. J., and Connor, J. A. (1992). Long-term depression of glutamate currents in cultured cerebellar Purkinje neurons does not require nitric oxide signalling. Eur. J. Neurosci.4:10–15. [DOI] [PubMed] [Google Scholar]
  96. Lipton, S. A., Choi, Y. B., Pan, Z. H., Lei, S. Z., Chen, H. S., Sucher, N. J., Loscalzo, J., Singel, D. J., and Stamler, J. S. (1993). A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature364:626–632. [DOI] [PubMed] [Google Scholar]
  97. Manzoni, O., Prezeau, L., Marin, P., Deshager, S., Bockaert, J., and Fagni, L. (1992). Nitric oxide-induced blockade of NMDA receptors. Neuron8:653–662. [DOI] [PubMed] [Google Scholar]
  98. Marras, R. A., Martins, A. P., Del Bel, E. A., and Guimaraes, F. S. (1995). L-NOARG, an inhibitor of nitric oxide synthase, induces catalepsy in mice. Neuroreport7:158–160. [PubMed] [Google Scholar]
  99. Meffert, M. K., Premack, B. A., and Schulman, H. (1994). Nitric oxide stimulates Ca(2+)-independent synaptic vesicle release. Neuron12:1235–1244. [DOI] [PubMed] [Google Scholar]
  100. Mitchell, I. J., Clarke, C. E., Boyce, S., Robertson, R. G., Peggs, D., Sambrook, M. A., and Crossman, A. R. (1989). Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience32:213–226. [DOI] [PubMed] [Google Scholar]
  101. Mollace, V., Bagetta, G., and Nistico, G. (1991). Evidence that L-arginine possesses proconvulsant effects mediated through nitric oxide. Neuroreport2:269–272. [DOI] [PubMed] [Google Scholar]
  102. Moore, N. A., Blackman, A., Awere, S., and Leander, J. D. (1993). NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists. Eur. J. Pharmacol.237:1–7. [DOI] [PubMed] [Google Scholar]
  103. Morris, B. J., Hollt, V., and Herz, A. (1988). Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: Contrasting effects of D1 and D2 antagonists. Neuroscience25:525–532. [DOI] [PubMed] [Google Scholar]
  104. Morris, B. J., Simpson, C. S., Mundell, S., Maceachern, K., Johnston, H. M., and Nolan, A. M. (1997). Dynamic changes in NADPH-diaphorase staining reflect activity of nitric oxide synthase: Evidence for a dopaminergic regulation of striatal nitric oxide release. Neuropharmacology36:1589–1599. [DOI] [PubMed] [Google Scholar]
  105. Mufson, E. J., and Brandabur, M. M. (1994). Sparing of NADPH-diaphorase striatal neurons in Parkinson’s and Alzheimer’s diseases. Neuroreport5:705–708. [DOI] [PubMed] [Google Scholar]
  106. Navarro, J. F., Vera, F., Manzaneque, J. M., Martín-López, M., Santiín, L. J., and Pedraza, C. (1997). Tolerance to the cataleptic effect of L-NOARG after subchronic administration in female mice. Med. Sci. Res.25:625–626. [Google Scholar]
  107. Ninan, I., and Kulkarni, S. K. (1999). Quinpirole, 8-OH-DPAT and ketanserin modulate catalepsy induced by high doses of atypical antipsychotics. Methods Find. Exp. Clin. Pharmacol.21:603–608. [PubMed] [Google Scholar]
  108. Noda, Y., Yamada, K., Furukawa, H., and Nabeshima, T. (1995). Involvement of nitric oxide in phencyclidine-induced hyperlocomotion in mice. Eur. J. Pharmacol.286:291–297. [DOI] [PubMed] [Google Scholar]
  109. Nucci-da-Silva, L. P., Guimaraes, F. S., and Del Bel, E. A. (1999). Serotonin modulation of catalepsy induced by N(G)-nitro-L-arginine in mice. Eur. J. Pharmacol.379:47–52. [DOI] [PubMed] [Google Scholar]
  110. O’Dell, T. J., Hawkins, R. D., Kandel, E. R., and Arancio, O. (1991). Tests of the roles of two diffusible substances in long-term potentiation: Evidence for nitric oxide as a possible early retrograde messenger. Proc. Natl. Acad. Sci. U.S.A.88:11285–11289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  111. Oka, M., Yamada, K., Kamei, C., Yoshida, K., and Shimizu, M. (1979). Differential antagonism of antiavoidance, cataleptic and ptotic effects of neuroleptics by biperiden. Jpn. J. Pharmacol.29:435–445. [DOI] [PubMed] [Google Scholar]
  112. Onstott, D., Mayer, B., and Beitz, A. J. (1993). Nitric oxide synthase immunoreactive neurons anatomically define a longitudinal dorsolateral column within the midbrain periaqueductal gray of the rat: Analysis using laser confocal microscopy. Brain Res.610:317–324. [DOI] [PubMed] [Google Scholar]
  113. Osborne, P. G., O’Connor, W. T., Beck, O., and Ungerstedt, U. (1994). Acute versus chronic haloperidol: Relationship between tolerance to catalepsy and striatal and accumbens dopamine, GABA and acetylcholine release. Brain Res.634:20–30. [DOI] [PubMed] [Google Scholar]
  114. Papa, S. M., Engber, T. M., Boldry, R. C., and Chase, T. N. (1993). Opposite effects of NMDA and AMPA receptor blockade on catalepsy induced by dopamine receptor antagonists. Eur. J. Pharmacol.232:247–253. [DOI] [PubMed] [Google Scholar]
  115. Ponzoni, S., Guimaraes, F. S., Del Bel, E. A., and Garcia-Cairasco, N. (2000). Behavioral effects of intra-nigral microinjections of manganese chloride: Interaction with nitric oxide. Prog .Neuropsychopharmacol. Biol. Psychiatry24:307–325. [DOI] [PubMed] [Google Scholar]
  116. Prinssen, E. P., Colpaert, F. C., and Koek, W. (2002). 5-HT1A receptor activation and anti-cataleptic effects: High-efficacy agonists maximally inhibit haloperidol-induced catalepsy. Eur. J. Pharmacol.453:217–221. [DOI] [PubMed] [Google Scholar]
  117. Pycock, C., Dawbarn, D., and O’Shaughnessy, C. (1982). Behavioural and biochemical changes following chronic administration of L-dopa to rats. Eur. J. Pharmacol.79:201–215. [DOI] [PubMed] [Google Scholar]
  118. Pycock, C. J. (1980). Turning behaviour in animals. Neuroscience5:461–514. [DOI] [PubMed] [Google Scholar]
  119. Quock, R. M., and Nguyen, E. (1992). Possible involvement of nitric oxide in chlordiazepoxide-induced anxiolysis in mice. Life Sci.51:L255–L260. [DOI] [PubMed] [Google Scholar]
  120. Rosa, W. C., Oliveira, G. M., and Nakamura-Palacios, E. M. (1994). Effects of the antihypertensive drugs alpha-methyldopa and hydralazine on the performance of spontaneously hypertensive rats in the elevated plus-maze. Braz. J. Med. Biol. Res.27:55–59. [PubMed] [Google Scholar]
  121. Royland, J. E., Delfani, K., Langston, J. W., Janson, A. M., and Di Monte, D. A. (1999). 7-Nitroindazole prevents 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced ATP loss in the mouse striatum. Brain Res.839:41–48. [DOI] [PubMed] [Google Scholar]
  122. Salter, M., Duffy, C., and Hazelwood, R. (1995). Determination of brain nitric oxide synthase inhibition in vivo: Ex vivo assays of nitric oxide synthase can give incorrect results. Neuropharmacology34:327–334. [DOI] [PubMed] [Google Scholar]
  123. Sanberg, P. R., Bunsey, M. D., Giordano, M., and Norman, A. B. (1988). The catalepsy test: Its ups and downs. Behav. Neurosci.102:748–759. [DOI] [PubMed] [Google Scholar]
  124. Sanberg, P. R., Pevsner, J., and Coyle, J. T. (1984). Parametric influences on catalepsy. Psychopharmacology (Berl)82:406–408. [DOI] [PubMed] [Google Scholar]
  125. Sanberg, P. R., Pisa, M., Faulks, I. J., and Fibiger, H. C. (1980). Experimental influences on catalepsy. Psychopharmacology (Berl)69:225–226. [DOI] [PubMed] [Google Scholar]
  126. Sandi, C., Venero, C., and Guaza, C. (1995). Decreased spontaneous motor activity and startle response in nitric oxide synthase inhibitor-treated rats. Eur. J. Pharmacol.277:89–97. [DOI] [PubMed] [Google Scholar]
  127. Sandor, N. T., Brassai, A., Puskas, A., and Lendvai, B. (1995). Role of nitric oxide in modulating neurotransmitter release from rat striatum. Brain Res. Bull.36:483–486. [DOI] [PubMed] [Google Scholar]
  128. Saner, A., and Thoenen, H. (1971). Model experiments on the molecular mechanism of action of 6-hydroxydopamine. Mol. Pharmacol.7:147–154. [PubMed] [Google Scholar]
  129. Sardo, P., Ferraro, G., Di Giovanni, G., Galati, S., and La, G. V. (2002). Inhibition of nitric oxide synthase influences the activity of striatal neurons in the rat. Neurosci. Lett.325:179–182. [DOI] [PubMed] [Google Scholar]
  130. Schmidt, H. H., Gagne, G. D., Nakane, M., Pollock, J. S., Miller, M. F., and Murad, F. (1992). Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J. Histochem. Cytochem.40:1439–1456. [DOI] [PubMed] [Google Scholar]
  131. Shibuki, K., and Okada, D. (1991). Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature349:326–328. [DOI] [PubMed] [Google Scholar]
  132. Silva, M. T., Rose, S., Hindmarsh, J. G., Aislaitner, G., Gorrod, J. W., Moore, P. K., Jenner, P., and Marsden, C. D. (1995). Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7-nitro indazole. Br. J. Pharmacol.114:257–258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  133. Silva, M. T., Rose, S., Hindmarsh, J. G., and Jenner, P. (2003). Inhibition of neuronal nitric oxide synthase increases dopamine efflux from rat striatum. J. Neural Transm.110:353–362. [DOI] [PubMed] [Google Scholar]
  134. Sistiaga, A., Miras-Portugal, M. T., and Sanchez-Prieto, J. (1997). Modulation of glutamate release by a nitric oxide/cyclic GMP-dependent pathway. Eur. J. Pharmacol.321:247–257. [DOI] [PubMed] [Google Scholar]
  135. Starr, M. S., and Starr, B. S. (1995). Do NMDA receptor-mediated changes in motor behaviour involve nitric oxide? Eur. J. Pharmacol.272:211–217. [DOI] [PubMed] [Google Scholar]
  136. Stewart, T. L., Michel, A. D., Black, M. D., and Humphrey, P. P. (1996). Evidence that nitric oxide causes calcium-independent release of [3H] dopamine from rat striatum in vitro. J. Neurochem.66:131–137. [DOI] [PubMed] [Google Scholar]
  137. Sugaya, K., and McKinney, M. (1994). Nitric oxide synthase gene expression in cholinergic neurons in the rat brain examined by combined immunocytochemistry and in situ hybridization histochemistry. Brain Res. Mol. Brain Res.23:111–125. [DOI] [PubMed] [Google Scholar]
  138. Traystman, R. J., Moore, L. E., Helfaer, M. A., Davis, S., Banasiak, K., Williams, M., and Hurn, P. D. (1995). Nitro-L-arginine analogues. Dose- and time-related nitric oxide synthase inhibition in brain. Stroke26:864–869. [DOI] [PubMed] [Google Scholar]
  139. Ungerstedt, U. (1968). 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol.5:107–110. [DOI] [PubMed] [Google Scholar]
  140. Ungerstedt, U. (1971a). Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand. Suppl367:69–93. [DOI] [PubMed] [Google Scholar]
  141. Ungerstedt, U. (1971b). Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand. Suppl367:49–68. [DOI] [PubMed] [Google Scholar]
  142. Ushijima, I., Kawano, M., Kaneyuki, H., Suetsugi, M., Usami, K., Hirano, H., Mizuki, Y., and Yamada, M. (1997). Dopaminergic and cholinergic interaction in cataleptic responses in mice. Pharmacol. Biochem. Behav.58:103–108. [DOI] [PubMed] [Google Scholar]
  143. Uzbay, I. T. (2001). L-NAME precipitates catatonia during ethanol withdrawal in rats. Behav. Brain Res.119:71–76. [DOI] [PubMed] [Google Scholar]
  144. Vale, A. L., Green, S., Montgomery, A. M., and Shafi, S. (1998). The nitric oxide synthesis inhibitor L-NAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test. J. Psychopharmacol.12:268–272. [DOI] [PubMed] [Google Scholar]
  145. Vincent, S. R., and Kimura, H. (1992). Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience46:755–784. [DOI] [PubMed] [Google Scholar]
  146. Volke, V., Koks, S., Vasar, E., Bourin, M., Bradwejn, J., and Mannisto, P. T. (1995). Inhibition of nitric oxide synthase causes anxiolytic-like behaviour in an elevated plus-maze. Neuroreport6:1413–1416. [DOI] [PubMed] [Google Scholar]
  147. West, A. R., and Galloway, M. P. (1998). Nitric oxide and potassium chloride-facilitated striatal dopamine efflux in vivo: Role of calcium-dependent release mechanisms. Neurochem. Int.33:493–501. [DOI] [PubMed] [Google Scholar]
  148. West, A. R., Galloway, M. P., and Grace, A. A. (2002). Regulation of striatal dopamine neurotransmission by nitric oxide: Effector pathways and Signaling mechanisms. Synapse44:227–245. [DOI] [PubMed] [Google Scholar]
  149. Wichmann, T., and DeLong, M. R. (1996). Functional and pathophysiological models of the basal ganglia. Curr. Opin. Neurobiol.6:751–758. [DOI] [PubMed] [Google Scholar]
  150. Yildiz, F., Ulak, G., Erden, B. F., and Gacar, N. (2000). Anxiolytic-like effects of 7-nitroindazole in the rat plus-maze test. Pharmacol. Biochem. Behav.65:199–202. [DOI] [PubMed] [Google Scholar]
  151. Yoshida, Y., Ono, T., Kawano, K., and Miyagishi, T. (1994). Distinct sites of dopaminergic and glutamatergic regulation of haloperidol-induced catalepsy within the rat caudate-putamen. Brain Res.639:139–148. [DOI] [PubMed] [Google Scholar]
  152. Zarrindast, M. R., Modabber, M., and Sabetkasai, M. (1993). Influences of different adenosine receptor subtypes on catalepsy in mice. Psychopharmacology (Berl)113:257–261. [DOI] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES