Abstract
Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson’s disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D1 receptors (D1Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D1Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D1R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D1R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D1R agonist to prevent and reverse the effect of the D1R antagonist in beam-walking scores is an indicator that the function of D1Rs is necessary to maintain motor coordination and balance in rats. Our results support that D1Rs mediate the SCH-23390-induced deficit in motor coordination.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agmo A, Soria P (1999) The duration of the effects of a single administration of dopamine antagonists on ambulatory activity and motor coordination. J Neural Transm (Vienna, Austria : 1996) 106:219–227. https://doi.org/10.1007/s007020050152
Albin RL, Young AB, Penney JB (1989) The functional-anatomy of basal ganglia disorders. Trends Neurosci 12:366–375. https://doi.org/10.1016/0166-2236(89)90074-x
Andersen PH, Jansen JA (1990) Dopamine receptor agonists - selectivity and dopamine-D1 receptor efficacy. Eur J Pharmacol Mol Pharm Sect 188:335–347. https://doi.org/10.1016/0922-4106(90)90194-3
Avila-Luna A, Prieto-Leyva J, Galvez-Rosas A, Alfaro-Rodriguez A, Gonzalez-Pina R, Bueno-Nava A (2015) D-1 antagonists and D-2 agonists have opposite effects on the metabolism of dopamine in the rat striatum. Neurochem Res 40:1431–1437. https://doi.org/10.1007/s11064-015-1611-4
Barili P, Bronzetti E, Ricci A, Zaccheo D, Amenta F (2000) Microanatomical localization of dopamine receptor protein immunoreactivity in the rat cerebellar cortex. Brain Res 854:130–138. https://doi.org/10.1016/s0006-8993(99)02306-9
Bergson C, Mrzljak L, Smiley JF, Pappy M, Levenson R, Goldman-Rakic PS (1995) Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. J Neurosci Off J Soc Neurosci 15:7821–7836
Bjorklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends Neurosci 30:194–202. https://doi.org/10.1016/j.tins.2007.03.006
Bostan AC, Strick PL (2010) The cerebellum and basal ganglia are interconnected. Neuropsychol Rev 20:261–270. https://doi.org/10.1007/s11065-010-9143-9
Bueno-Nava A, Gonzalez-Pina R, Alfaro-Rodriguez A, Nekrassov-Protasova V, Durand-Rivera A, Montes S, Ayala-Guerrero F (2010) Recovery of motor deficit, cerebellar serotonin and lipid peroxidation levels in the cortex of injured rats. Neurochem Res 35:1538–1545. https://doi.org/10.1007/s11064-010-0213-4
Bueno-Nava A, Gonzalez-Pina R, Alfaro-Rodriguez A, Avila-Luna A, Arch-Tirado E, Alonso-Spilsbury M (2012) The selective inhibition of the D-1 dopamine receptor results in an increase of metabolized dopamine in the rat striatum. Neurochem Res 37:1783–1789. https://doi.org/10.1007/s11064-012-0790-5
Camps M, Kelly PH, Palacios JM (1990) Autoradiographic localization of dopamine D 1 and D 2 receptors in the brain of several mammalian species. J Neural Transm Gen Sect 80:105–127. https://doi.org/10.1007/bf01257077
Chagniel L, Robitaille C, Lacharite-Mueller C, Bureau G, Cyr M (2012) Partial dopamine depletion in MPTP-treated mice differentially altered motor skill learning and action control. Behav Brain Res 228:9–15. https://doi.org/10.1016/j.bbr.2011.11.019
Costa RM, Lin S-C, Sotnikova TD, Cyr M, Gainetdinov RR, Caron MG, Nicolelis MAL (2006) Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction. Neuron 52:359–369. https://doi.org/10.1016/j.neuron.2006.07.030
Curtze C, Nutt JG, Carlson-Kuhta P, Mancini M, Horak FB (2015) Levodopa is a double-edged sword for balance and gait in people with Parkinson's disease. Mov Disord 30:1361–1370. https://doi.org/10.1002/mds.26269
Dalton A, Khalil H, Busse M, Rosser A, van Deursen R, Olaighin G (2013) Analysis of gait and balance through a single triaxial accelerometer in presymptomatic and symptomatic. Huntington's Dis Gait & Posture 37:49–54. https://doi.org/10.1016/j.gaitpost.2012.05.028
Daskalakis ZJ, Paradiso GO, Christensen BK, Fitzgerald PB, Gunraj C, Chen R (2004) Exploring the connectivity between the cerebellum and motor cortex in humans. J Physiol 557:689–700. https://doi.org/10.1113/jphysiol.2003.059808
De Vasconcelos AP, Klur S, Muller C, Csquer B, Lopez J, Certa U, Cassel JC (2006) Reversible inactivation of the dorsal hippocampus by tetrodotoxin or lidocaine: a comparative study on cerebral functional activity and motor coordination in the rat. Neuroscience 141:1649–1663. https://doi.org/10.1016/j.neuroscience.2006.05.023
Doya K (2000) Complementary roles of basal ganglia and cerebellum in learning and motor control. Curr Opin Neurobiol 10:732–739. https://doi.org/10.1016/s0959-4388(00)00153-7
Festing MF (1994) Reduction of animal use: experimental design and quality of experiments. Lab Anim 28:212–221. https://doi.org/10.1258/002367794780681697
Grabli D et al (2013) Gait disorders in parkinsonian monkeys with Pedunculopontine nucleus lesions: a tale of two systems. J Neurosci 33:11986–11993. https://doi.org/10.1523/jneurosci.1568-13.2013
Imperato A, Mulas A, Di Chiara G (1987) The D-1 antagonist SCH 23390 stimulates while the D-1 agonist SKF 38393 fails to affect dopamine release in the dorsal caudate of freely moving rats. Eur J Pharmacol 142:177–181. https://doi.org/10.1016/0014-2999(87)90672-8
Izenwasser S, Katz JL (1993) Differential efficacies of dopamine D1 receptor agonists for stimulating adenylyl-cyclase in squirrel-monkey and rat. Eur J Pharmacol Mol Pharm Sect 246:39–44. https://doi.org/10.1016/0922-4106(93)90007-v
Mendoza G, Merchant H (2014) Motor system evolution and the emergence of high cognitive functions. Prog Neurobiol 122:73–93. https://doi.org/10.1016/j.pneurobio.2014.09.001
Molloy AG, Waddington JL (1984) Dopaminergic behavior stereospecifically promoted by the D1 agonist r-sk-and-f-38393 and selectively blocked by the D1 antagonist SCH-23390. Psychopharmacology 82:409–410. https://doi.org/10.1007/bf00427697
Nowak P et al (2008) Histamine H(3) receptor ligands modulate L-DOPA-evoked behavioral responses and L-DOPA-derived extracellular dopamine in dopamine-denervated rat striatum. Neurotox Res 13:231–240
Olfert E, Cross B, Mc William A (1993) Guide for the care and use of experimental animals. Can Council Animal Care 1:211
Rapanelli M (2017) The magnificent two: histamine and the H3 receptor as key modulators of striatal circuitry. Prog Neuro-Psychopharmacol Biol Psychiatry 73:36–40. https://doi.org/10.1016/j.pnpbp.2016.10.002
Rapanelli M, Frick LR, Horn KD, Schwarcz RC, Pogorelov V, Nairn AC, Pittenger C (2016) The histamine H3 receptor differentially modulates mitogen-activated protein kinase (MAPK) and Akt signaling in Striatonigral and Striatopallidal neurons. J Biol Chem 291:21042–21052. https://doi.org/10.1074/jbc.M116.731406
Surmeier DJ, Song WJ, Yan Z (1996) Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci Off J Soc Neurosci 16:6579–6591
Takakusaki K, Tomita N, Yano M (2008) Substrates for normal gait and pathophysiology of gait disturbances with respect to the basal ganglia dysfunction. J Neurol 255:19–29. https://doi.org/10.1007/s00415-008-4004-7
Wang JQ, McGinty JF (1996) Scopolamine augments C-fos and ZIF/268 messenger RNA expression induced by the full D-1 dopamine receptor agonist SKF-82958 in the intact rat striatum. Neuroscience 72:601–616. https://doi.org/10.1016/0306-4522(95)00597-8
Acknowledgements
The authors thank Dr. Iván Pérez-Neri for his assistance in performing the recordings of spontaneous activity. We thank MVZ Hugo Lecona Butrón for support with the housing, care, maintenance and monitoring of the health of the experimental animals in the institute (INR-LGII). We thank MVZ Javier Pérez Gallaga for technical support.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Supplementary video 1
Effect of the systemic administration of the D1R agonist SKF-38393 alone, the administration of the antagonist SCH-23390 alone and the co-administration of SKF-38393 + SCH-23390. Note the null effect of the administration of SKF-38393 alone and the motor coordination deficit induced by SCH-23390. The co-administration of SKF-38393 + SCH-23390 indicates that the motor coordination is mediated by D1Rs. (MP4 94,640 kb)
Rights and permissions
About this article
Cite this article
Avila-Luna, A., Gálvez-Rosas, A., Durand-Rivera, A. et al. Dopamine D1 receptor activation maintains motor coordination and balance in rats. Metab Brain Dis 33, 99–105 (2018). https://doi.org/10.1007/s11011-017-0126-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-017-0126-x