Advertisement

Neuroscience and Behavioral Physiology

, Volume 44, Issue 9, pp 1014–1019 | Cite as

Comparative Analysis of the Effects of Blockade of Striatal Metabotropic and Ionotropic Glutamate Receptors on Motor Behavior in Rats

  • A. F. Yakimovskii
  • T. V. Kerko
Article
  • 26 Downloads

Chronic experiments on rats addressed the effects of blockade of NMDA and metabotropic glutamate receptors in the neostriatum on conditioned reflex avoidance (in a shuttle box) and spontaneous (in an open field) behavior. Glutamate receptor antagonists were given bilaterally into the neostriatum, in some experiments with the GABAA receptor antagonist picrotoxin (2 μg), which impairs execution of conditioned reflex skills and produces choreomyoclonic hyperkinesia. The most effective agent in preventing the adverse effects of picrotoxin on behavior was the type 5 metabotropic receptor antagonist MTEP (3 μg), which when given into the neostriatum without picrotoxin had no effect on measures of avoidance behavior and did not alter the level of spontaneous motor activity. In contrast, the type 1 metabotropic receptor antagonist EMQMCM (3 μg) degraded measures of normal motor behavior (indicative of a sedative effect) but did not prevent the actions of picrotoxin. The NMDA receptor antagonist MK-801 (dizocilpine, 1 and 5 μg) decreased picrotoxin-induced hyperkinesia but had only mild effects on its adverse influence on conditioned reflex activity; given alone into the striatum, it decreased normal motor activity. Considering the distributions of the study receptors on neostriatal neuron membranes, it is suggested that the most effective action, on type 5 glutamate receptors, may be linked with their involvement in supporting the activity of the “indirect” efferent pathway, the activity of which is impaired in the hyperkinetic type of dysfunction of the extrapyramidal motor system in Huntington’s chorea in humans.

Keywords

neostriatum motor behavior hyperkinesia dizocilpine picrotoxin glutamate receptors 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    N. I. Dubrovina and D. R. Zinov’ev, “Effects of Dizocilpine on quenching of a conditioned passive avoidance reaction in mice with a depression-like state,” Byul. Sib. Otd. Rus. Akad. Med. Nauk., 125, No. 3, 25–29 (2007).Google Scholar
  2. 2.
    S. N. Illarioshkin, Conformational Diseases of the Brain,, Yanus-K, Moscow (2003).Google Scholar
  3. 3.
    Yu. A. Novitskaya, O. A. Dravolina, E. E. Zvartau, and V. Danish, “Interaction of ionotropic NMDA receptor blockers and metabotropic glutamate receptors in a working memory test in rats,” Zh. Vyssh. Nerv. Deyat., 59, No. 4, 446–452 (2009).Google Scholar
  4. 4.
    I. G. Sil’kis, “Interaction of biochemical process in striatal neurons evoked by activation of excitatory, inhibitory, and dopamine inputs,” Ros. Fiziol. Zh., 86, No. 5, 507–518 (2002).Google Scholar
  5. 5.
    N. F. Suvorov and V. T. Shuvaev, “Involvement of the basal ganglia in organizing behavior,” Ros. Fiziol., 88, No. 10, 1233–1240 (2002).Google Scholar
  6. 6.
    A. F. Yakimovskii, “A method for prolonged local actions on neurotransmitter systems in the nuclei of the brain,” Fiziol. Zh. SSSR, 74, No. 3, 745–751 (1988).Google Scholar
  7. 7.
    A. F. Yakimovskii, “Myoclonic hyperkinesia induced by repeated administration of picrotoxin into the neostriatum in rats,” Byull. Eksperim. Biol. Med., 114, No. 1, 7–9 (1993).Google Scholar
  8. 8.
    A. F. Yakimovskii, “Functional specialization of transmitter systems as the basis for the multifunctionality of the neostriatum,” Ros. Fiziol. Zh., 84, No. 9, 906–912 (1998).Google Scholar
  9. 9.
    D. M. Ashby, D. Habib, H. C. Dringenberg, et al., “Subchronic MK-801 treatment and post-weaning social isolation in rats: differential effects on locomotor activity and hippocampal long-term potentiation,” Behav. Brain Res., 212, No. 1, 64–70 (2010).CrossRefPubMedGoogle Scholar
  10. 10.
    I. Bezprozvanny and M. R. Hayden, “Deranged neuronal calcium signaling and Huntington disease,” Biochem. Biophys. Res. Commun., 322, No. 4, 1310–1317 (2004).CrossRefPubMedGoogle Scholar
  11. 11.
    P. Calabresi, D. Centonze, P. Gubellini, et al., “Synaptic transmission in the striatum: from plasticity to neurodegeneration,” Progr. Neurobiol., 61, No. 3, 231–265 (2000).CrossRefGoogle Scholar
  12. 12.
    P. J. Conn, G. Battaglia, M. J. Marino, and F. Nicoletti, “Metabotropic glutamate receptors in the basal ganglia motor circuit,” Nat. Rev. Neurosci., 6, No. 10, 787–798 (2005).CrossRefPubMedGoogle Scholar
  13. 13.
    F. Ferraguti, L. Crepaldi, and F. Nicoletti, “Metabotropic glutamate 1 receptor: current concepts and perspectives,” Pharmacol. Rev., 60, No. 4, 536–581 (2008).CrossRefPubMedGoogle Scholar
  14. 14.
    A. Galvan, M. Kuwajima, and Y. Smith, “Glutamate and GABA receptors and transporters in the basal ganglia: What does their subsynaptic localization reveal about their function?” Neuroscience, 143, No. 2, 351–375 (2006).CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    A. Gravius, B. Pietraszeka, D. Schafera, et al., “Effects of mGlu1 and mGlu5 receptor antagonists on negatively reinforced learning,” Behav. Pharmacol., 16, No. 2, 113–121 (2005).CrossRefPubMedGoogle Scholar
  16. 16.
    A. M. Graybiel, “The basal ganglia and chunking of action repertoires,” Neurobiol. Learn. Mem., 70, No. 2, 119–136 (1998).CrossRefPubMedGoogle Scholar
  17. 17.
    Y.-J. I. Jong, V. Kumar, A. E. Kingston, et al., “Functional metabotropic glutamate receptors on nuclei from brain and primary cultured striatal neurons: role of transporters in delivering ligand,” J. Biol. Chem., 280, No. 34, 30,469–30,480 (2005).CrossRefGoogle Scholar
  18. 18.
    H. Kalonia, P. Kumar, B. Nehru, and A. Kumar, “Neuroprotective effect of MK-801 against intra-striatal quinolinic acid induced behavioral, oxidative stress and cellular alterations in rats,” Ind. J. Exp. Biol., 47, No. 11, 880–892 (2009).Google Scholar
  19. 19.
    M. Paquet and Y. Smith, “Group I metabotropic glutamate receptors in the monkey striatum: subsynaptic association with glutamatergic and dopaminergic afferents,” J. Neurosci., 23, No. 20, 7659–7669 (2003).PubMedGoogle Scholar
  20. 20.
    A. Pisani, P. Bonsi, D. Centonze, et al., “Targeting striatal cholinergic interneurons in Parkinson’s disease: focus on metabotropic glutamate receptors,” Neuropharmacology, 456, No. 11, 45–56 (2003).CrossRefGoogle Scholar
  21. 21.
    S. Y. Sakurai, J.-H. J. Cha, J. B. Penney, and A. B. Young, “Regional distribution and properties of [3H]MK-801 binding sites determined by quantitative autoradiography in rat brain,” Neuroscience, 40, No. 2, 533–543 (1991).CrossRefPubMedGoogle Scholar
  22. 22.
    Y. Smith, A. Charara, M. Paquet, et al., “Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia,” J. Chem. Neuroanat., 22, No. 1, 13–42 (2001).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.St. Petersburg State Medical UniversitySt. PetersburgRussia
  2. 2.Institute of PhysiologyRussian Academy of SciencesSt. PetersburgRussia

Personalised recommendations