Lesion of Subthalamic Nucleus in Parkinsonian Rats : Effects of Dopamine $D_1$ and $D_2$ Receptor Agonists on the Neuronal Activities of the Substantia Nigra Pars Reticulata

  • Park, Yong-Sook (Department of Neurosurgery Chung-Ang University College of Medicine) ;
  • Jeon, Mi-Fa (Department of Brain Research Institute Yonsei University College of Medicine) ;
  • Lee, Bae-Hwan (Department of Brain Research Institute Yonsei University College of Medicine) ;
  • Chang, Jin-Woo (Department of Neurosurgery Brain Korea 21 Project for Medical Science & Yonsei University College of Medicine)
  • Published : 2007.12.28

Abstract

Objective : It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a $D_1$ receptor agonist) and Quinpirole (a $D_2$ receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. Methods : SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. Results : The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. Conclusion : This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of $D_1$ and $D_2$ agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and $D_1$, $D_2$ selective antagonist.

Keywords

References

  1. Albin RL, Young AB, Penney JB : The functional anatomy of basal ganglia disorders. Trends Neurosci 12 : 366-375, 1989 https://doi.org/10.1016/0166-2236(89)90074-X
  2. Bergman H, Wichmann T, Karmon B, DeLong MR : The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 72 : 507-520, 1994 https://doi.org/10.1152/jn.1994.72.2.507
  3. Bertorello AM, Hopfield JF, Aperia A, Greengard P : Inhibition by dopamine of (Na(+)+K+)ATPase activity in neostriatal neurons through $D_{1}$ and $D_{2}$ dopamine receptor synergism. Nature 347 : 386-388, 1990 https://doi.org/10.1038/347386a0
  4. Burbaud P, Gross C, Benazzouz A, Coussemacq M, Bioulac B : Reduction of apomorphine-induced rotational behaviour by subthalamic lesion in 6-OHDA lesioned rats is associated with a normalization of firing rate and discharge pattern of pars reticulata neurons. Exp Brain Res 105 : 48-58, 1995
  5. Calabresi P, Maj R, Mercuri NB, Bernardi G : Coactivation of $D_{1}$ and $D_{2}$ dopamine receptors is required for long-term synaptic depression in the striatum. Neurosci Lett 142 : 95-99, 1992 https://doi.org/10.1016/0304-3940(92)90628-K
  6. DeLong MR : Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13 : 281-285, 1990 https://doi.org/10.1016/0166-2236(90)90110-V
  7. Gerfen CR, Keefe KA, Gauda EB : $D_{1}$ and $D_{2}$ dopamine receptor function in the striatum : coactivation of $D_{1}$- and $D_{2}$-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in $D_{1}$-containing neurons. J Neurosci 15 : 8167- 8176, 1995 https://doi.org/10.1523/JNEUROSCI.15-12-08167.1995
  8. Hollerman JR, Grace AA : Subthalamic nucleus cell firing in the 6- OHDA-treated rat : basal activity and response to haloperidol. Brain Res 590 : 291-299, 1992 https://doi.org/10.1016/0006-8993(92)91108-Q
  9. Hu XT, Wang RY : Comparison of effects of $D-_{1}$ and $D-_{2}$ dopamine receptor agonists on neurons in the rat caudate putamen : an electrophysiological study. J Neurosci 8 : 4340-4348, 1988 https://doi.org/10.1523/JNEUROSCI.08-11-04340.1988
  10. Hutchison WD, Allan RJ, Opitz H, Levy R, Dostrovsky JO, Lang AE, et al : Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease. Ann Neurol 44 : 622-628, 1998 https://doi.org/10.1002/ana.410440407
  11. Hutchison WD, Levy R, Dostrovsky JO, Lozano AM, Lang AE : Effects of apomorphine on globus pallidus neurons in parkinsonian patients. Ann Neurol 42 : 767-775, 1997 https://doi.org/10.1002/ana.410420513
  12. Jeon MF, Ha Y, Cho YH, Lee BH, Park YG, Chang JW : Effect of ipsilateral subthalamic nucleus lesioning in a rat parkinsonian model : study of behavior correlated with neuronal activity in the pedunculopontine nucleus. J Neurosurg 99 : 762-767, 2003 https://doi.org/10.3171/jns.2003.99.4.0762
  13. Kreiss DS, Mastropietro CW, Rawji SS, Walters JR : The response of subthalamic nucleus neurons to dopamine receptor stimulation in a rodent model of Parkinson's disease. J Neurosci 17 : 6807-6819, 1997 https://doi.org/10.1523/JNEUROSCI.17-17-06807.1997
  14. Limousin P, Pollak P, Benazzouz A, Hoffmann D, Le Bas JF, Broussolle E, et al : Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet 345 : 91-95, 1995 https://doi.org/10.1016/S0140-6736(95)90062-4
  15. MacLeod NK, Ryman A, Arbuthnott GW : Electrophysiological properties of nigrothalamic neurons after 6-hydroxydopamine lesions in the rat. Neuroscience 38 : 447-456, 1990 https://doi.org/10.1016/0306-4522(90)90041-2
  16. Miller WC, DeLong MR : Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of Parkinsonism. The basal ganglia. II., in. New York : Plenum, 1987, Vol 32, pp415-427
  17. Murer MG, Riquelme LA, Tseng KY, Cristal A, Santos J, Pazo JH : $D_{1}$-$D_{2}$ dopamine receptor interaction : an in vivo single unit electrophysiological study. Neuroreport 8 : 783-787, 1997 https://doi.org/10.1097/00001756-199702100-00041
  18. Ni ZG, Bouali-Benazzouz R, Gao DM, Benabid AL, Benazzouz A : Time-course of changes in firing rates and firing patterns of subthalamic nucleus neuronal activity after 6-OHDA-induced dopamine depletion in rats. Brain Res 899 : 142-147, 2001 https://doi.org/10.1016/S0006-8993(01)02219-3
  19. Obeso JA, Olanow CW, Nutt JG : Levodopa motor complications in Parkinson's disease. Trends Neurosci 23 : S2-7, 2000 https://doi.org/10.1016/S1471-1931(00)00031-8
  20. Perier C, Marin C, Jimenez A, Bonastre M, Tolosa E, Hirsch EC : Effect of subthalamic nucleus or entopeduncular nucleus lesion on levodopa-induced neurochemical changes within the basal ganglia and on levodopa-induced motor alterations in 6-hydroxydopamine-lesioned rats. J Neurochem 86 : 1328-1337, 2003 https://doi.org/10.1046/j.1471-4159.2003.01960.x
  21. Piomelli D, Pilon C, Giros B, Sokoloff P, Martres MP, Schwartz JC : Dopamine activation of the arachidonic acid cascade as a basis for $D_{1}/D_{2}$ receptor synergism. Nature 353 : 164-167, 1991 https://doi.org/10.1038/353164a0
  22. Rohlfs A, Nikkhah G, Rosenthal C, Rundfeldt C, Brandis A, Samii M, et al : Hemispheric asymmetries in spontaneous firing characteristics of substantia nigra pars reticulata neurons following a unilateral 6- hydroxydopamine lesion of the rat nigrostriatal pathway. Brain Res 761 : 352-356, 1997 https://doi.org/10.1016/S0006-8993(97)00475-7
  23. Shen RY, Asdourian D, Chiodo LA : Microiontophoretic studies of the effects of $D-_{1}$ and $D-_{2}$ receptor agonists on type I caudate nucleus neurons : lack of synergistic interaction. Synapse 11 : 319-329, 1992 https://doi.org/10.1002/syn.890110407