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GABAergic imbalance is normalized by dopamine D1 receptor activation in the striatum contralateral to the cortical injury in motor deficit-recovered rats

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Abstract

Rationale

The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function, which may be modulated by dopamine.

Objectives

We studied whether the activation of dopamine D1 receptors (D1Rs) modulates the γ-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury.

Methods

The D1R agonist SKF-38393 (0, 2, 3, or 4 mg/kg) was administered at 24, 48, 96, and 192 h post-injury, and then rats were decapitated to determine GABA and glutamate levels and the levels of D1R mRNA on both sides of the striatum.

Results

GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D1R agonist, but this treatment did not produce a significant effect on glutamate levels, suggesting that glutamate was metabolized into GABA. The administration of SKF-38393 (2 mg/kg) decreased the levels of D1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D1R agonist increased the D1R mRNA levels, an effect that was blocked by SCH-23390.

Conclusion

The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal D1R activation, and the D1R agonist-induced increases in the D1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.

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Abbreviations

D1R:

dopamine D1 receptor

D2R:

dopamine D2 receptor

DA:

dopamine

GABA:

γ-aminobutyric acid

MSNs:

medium spiny neurons

TBI:

traumatic brain injury

SNc:

substantia nigra pars compacta

M1:

primary motor cortex

HPLC:

high-performance liquid chromatography

PKA:

protein kinase A

DARPP-32:

DA- and cAMP-regulated phosphoprotein 32

References

  • Abekawa T, Ohmori T, Ito K, Koyama T (2000) D1 dopamine receptor activation reduces extracellular glutamate and GABA concentrations in the medial prefrontal cortex. Brain Res 867:250–254

    Article  CAS  PubMed  Google Scholar 

  • Amorini AM, Lazzarino G, Di Pietro V, Signoretti S, Belli A, Tavazzi B (2017) Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids. J Cell Mol Med 21:530–542

    Article  CAS  PubMed  Google Scholar 

  • Avila-Luna A, Galvez-Rosas A, Alfaro-Rodriguez A, Reyes-Legorreta C, Garza-Montano P, Gonzalez-Pina R, Bueno-Nava A (2018a) Dopamine D1 receptor activation maintains motor coordination in injured rats but does not accelerate the recovery of the motor coordination deficit. Behav Brain Res 336:145–150

    Article  CAS  PubMed  Google Scholar 

  • Avila-Luna A, Galvez-Rosas A, Durand-Rivera A, Ramos-Languren LE, Rios C, Arias-Montano JA, Bueno-Nava A (2018b) Dopamine D1 receptor activation maintains motor coordination and balance in rats. Metab Brain Dis 33:99–105

    Article  CAS  PubMed  Google Scholar 

  • Bales JW, Wagner AK, Kline AE, Dixon CE (2009) Persistent cognitive dysfunction after traumatic brain injury: a dopamine hypothesis. Neurosci Biobehav Rev 33:981–1003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bales JW, Yan HQ, Ma X, Li Y, Samarasinghe R, Dixon CE (2011) The dopamine and cAMP regulated phosphoprotein, 32 kDa (DARPP-32) signaling pathway: a novel therapeutic target in traumatic brain injury. Exp Neurol 229:300–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 15:7821–7836

    Article  CAS  PubMed  Google Scholar 

  • Bjorklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends Neurosci 30:194–202

    Article  CAS  PubMed  Google Scholar 

  • Bostan AC, Strick PL (2010) The cerebellum and basal ganglia are interconnected. Neuropsychol Rev 20:261–270

    Article  PubMed  PubMed Central  Google Scholar 

  • Brailowsky S, Knight RT, Blood K, Scabini D (1986) Gamma-aminobutyric acid-induced potentiation of cortical hemiplegia. Brain Res 362:322–330

    Article  CAS  PubMed  Google Scholar 

  • Bueno-Nava A, Montes S, DelaGarza-Montano P, Alfaro-Rodriguez A, Ortiz A, Gonzalez-Pina R (2008) Reversal of noradrenergic depletion and lipid peroxidation in the pons after brain injury correlates with motor function recovery in rats. Neurosci Lett 443:32–36

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Bullock R, Zauner A, Woodward JJ, Myseros J, Choi SC, Ward JD, Marmarou A, Young HF (1998) Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg 89:507–518

    Article  CAS  PubMed  Google Scholar 

  • Bunzow JR, Van Tol HH, Grandy DK, Albert P, Salon J, Christie M, Machida CA, Neve KA, Civelli O (1988) Cloning and expression of a rat D2 dopamine receptor cDNA. Nature 336:783–787

    Article  CAS  PubMed  Google Scholar 

  • Camps M, Kelly PH, Palacios JM (1990) Autoradiographic localization of dopamine D1 and D2 receptors in the brain of several mammalian species. J Neural Transm Gen Sect 80:105–127

    Article  CAS  PubMed  Google Scholar 

  • Cantu D, Walker K, Andresen L, Taylor-Weiner A, Hampton D, Tesco G, Dulla CG (2015) Traumatic brain injury increases cortical glutamate network activity by compromising GABAergic control. Cereb Cortex 25:2306–2320

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Chamoun R, Suki D, Gopinath SP, Goodman JC, Robertson C (2010) Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury. J Neurosurg 113:564–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • De Beaumont L, Tremblay S, Poirier J, Lassonde M, Theoret H (2012) Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes. Cereb Cortex 22:112–121

    Article  PubMed  Google Scholar 

  • Ding J, Peterson JD, Surmeier DJ (2008) Corticostriatal and thalamostriatal synapses have distinctive properties. J Neurosci 28:6483–6492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doya K (2000) Complementary roles of basal ganglia and cerebellum in learning and motor control. Curr Opin Neurobiol 10:732–739

    Article  CAS  PubMed  Google Scholar 

  • Festing MF (1994) Reduction of animal use: experimental design and quality of experiments. Lab Anim 28:212–221

    Article  CAS  PubMed  Google Scholar 

  • Folkersma H, Foster Dingley JC, van Berckel BN, Rozemuller A, Boellaard R, Huisman MC, Lammertsma AA, Vandertop WP, Molthoff CF (2011) Increased cerebral (R)-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study. J Neuroinflammation 8:67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerfen CR, Surmeier DJ (2011) Modulation of striatal projection systems by dopamine. Annu Rev Neurosci 34(34):441–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guerriero RM, Giza CC, Rotenberg A (2015) Glutamate and GABA imbalance following traumatic brain injury. Curr Neurol Neurosci Rep 15:27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayes JP, Bigler ED, Verfaellie M (2016) Traumatic brain injury as a disorder of brain connectivity. J Int Neuropsychol Soc 22:120–137

    Article  PubMed  PubMed Central  Google Scholar 

  • Hinzman JM, Thomas TC, Burmeister JJ, Quintero JE, Huettl P, Pomerleau F, Gerhardt GA, Lifshitz J (2010) Diffuse brain injury elevates tonic glutamate levels and potassium-evoked glutamate release in discrete brain regions at two days post-injury: an enzyme-based microelectrode Array study. J Neurotrauma 27:889–899

    Article  PubMed  PubMed Central  Google Scholar 

  • Hinzman JM, Thomas TC, Quintero JE, Gerhardt GA, Lifshitz J (2012) Disruptions in the regulation of extracellular glutamate by neurons and glia in the rat striatum two days after diffuse brain injury. J Neurotrauma 29:1197–1208

    Article  PubMed  PubMed Central  Google Scholar 

  • Hoskison MM, Moore AN, Hu B, Orsi S, Koboric N, Dash PK (2009) Persistent working memory dysfunction following traumatic brain injury: evidence for a time-dependent mechanism. Neuroscience 159:483–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu KS, Huang CC, Yang CH, Gean PW (1995) Presynaptic D2 dopaminergic receptors mediate inhibition of excitatory synaptic transmission in rat neostriatum. Brain Res 690:264–268

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Li WL, Mamtilahun M, Song YY, Ma YY, Qu MJ, Lu YF, He XS, Zheng JY, Fu ZJ, Zhang ZJ, Yang GY, Wang YT (2017) Optogenetic inhibition of striatal GABAergic neuronal activity improves outcomes after ischemic brain injury. Stroke 48:3375–3383

    Article  CAS  PubMed  Google Scholar 

  • Kantak SS, Stinear JW, Buch ER, Cohen LG (2012) Rewiring the brain: potential role of the premotor cortex in motor control, learning, and recovery of function following brain injury. Neurorehabil Neural Repair 26:282–292

    Article  PubMed  Google Scholar 

  • Kerkerian L, Dusticier N, Nieoullon A (1987) Modulatory effect of dopamine on high-affinity glutamate uptake in the rat striatum. J Neurochem 48:1301–1306

    Article  CAS  PubMed  Google Scholar 

  • Krobert KA, Sutton RL, Feeney DM (1994) Spontaneous and amphetamine-evoked release of cerebellar noradrenaline after sensorimotor cortex contusion: an in vivo microdialysis study in the awake rat. J Neurochem 62:2233–2240

    Article  CAS  PubMed  Google Scholar 

  • Le Moine C, Bloch B (1995) D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. J Comp Neurol 355:418–426

    Article  PubMed  Google Scholar 

  • Lei WL, Jiao Y, Del Mar N, Reiner A (2004) Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats. J Neurosci 24:8289–8299

    Article  CAS  PubMed  Google Scholar 

  • Lidow MS, Goldmanrakic PS, Gallager DW, Rakic P (1991) Distribution of dopaminergic receptors in the primate cerebral-cortex—quantitative autoradiographic analysis using 3H raclopride, 3H spiperone and 3H SCH23390. Neuroscience 40:657–671

    Article  CAS  PubMed  Google Scholar 

  • López de Maturana R, Sánchez-Pernaute R (2010) Regulation of corticostriatal synaptic plasticity by G protein-coupled receptors. Cns Neurol Disord-Drug Targets 9:601–615

    Article  PubMed  Google Scholar 

  • Mathai A, Smith Y (2011) The corticostriatal and corticosubthalamic pathways: two entries, one target. So what? Front Syst Neurosci 5:1–10

  • Mendoza G, Merchant H (2014) Motor system evolution and the emergence of high cognitive functions. Prog Neurobiol 122:73–93

    Article  PubMed  Google Scholar 

  • Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78:189–225

    Article  CAS  PubMed  Google Scholar 

  • Montes S, Alcaraz-Zubeldia M, Muriel P, Rios C (2003) Role of manganese accumulation in increased brain glutamine of the cirrhotic rat. Neurochem Res 28:911–917

    Article  CAS  PubMed  Google Scholar 

  • Muly EC, Szigeti K, Goldman-Rakic PS (1998) D1 receptor in interneurons of macaque prefrontal cortex: distribution and subcellular localization. J Neurosci 18:10553–10565

    Article  CAS  PubMed  Google Scholar 

  • Olfert E, Cross B, Mc William A (1993) Guide for the care and use of experimental animals. Can Counc Anim Care 1:211

    Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, London

    Google Scholar 

  • Petroff OAC (2002) GABA and glutamate in the human brain. Neuroscientist 8:562–573

    Article  CAS  PubMed  Google Scholar 

  • Reep RL, Cheatwood JL, Corwin JV (2003) The associative striatum: organization of cortical projections to the dorsocentral striatum in rats. J Comp Neurol 467:271–292

    Article  PubMed  Google Scholar 

  • Reiner A, Hart NM, Lei WL, Deng YP (2010) Corticostriatal projection neurons - dichotomous types and dichotomous functions. Front Neuroanat 4:1–15

  • Shin SS, Bray ER, Zhang CQ, Dixon CE (2011) Traumatic brain injury reduces striatal tyrosine hydroxylase activity and potassium-evoked dopamine release in rats. Brain Res 1369:208–215

    Article  CAS  PubMed  Google Scholar 

  • Silberberg G, Bolam JP (2015) Local and afferent synaptic pathways in the striatal microcircuitry. Curr Opin Neurobiol 33:182–187

    Article  CAS  PubMed  Google Scholar 

  • Smith Y, Raju DV, Pare JF, Sidibe M (2004) The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci 27:520–527

    Article  CAS  PubMed  Google Scholar 

  • Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350:614–619

    Article  CAS  PubMed  Google Scholar 

  • Surmeier DJ, Song WJ, Yan Z (1996) Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci 16:6579–6591

    Article  CAS  PubMed  Google Scholar 

  • Surmeier DJ, Ding J, Day M, Wang Z, Shen W (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 30:228–235

    Article  CAS  PubMed  Google Scholar 

  • Tremblay S, Beaule V, Proulx S, Marjanska M, Doyon J, Lassonde M, Theoret H (2014) Multimodal assessment of primary motor cortex integrity following sport concussion in asymptomatic athletes. Clin Neurophysiol 125:1371–1379

    Article  PubMed  PubMed Central  Google Scholar 

  • Valjent E, Bertran-Gonzalez J, Herve D, Fisone G, Girault J-A (2009) Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice. Trends Neurosci 32:538–547

    Article  CAS  PubMed  Google Scholar 

  • Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614

    Article  PubMed  Google Scholar 

  • Vespa P, Prins M, Ronne-Engstrom E, Caron M, Shalmon E, Hovda DA, Martin NA, Becker DP (1998) Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study. J Neurosurg 89:971–982

    Article  CAS  PubMed  Google Scholar 

  • Wagner AK, Sokoloski JE, Ren D, Chen X, Khan AS, Zafonte RD, Michael AC, Dixon CE (2005) Controlled cortical impact injury affects dopaminergic transmission in the rat striatum. J Neurochem 95:457–465

    Article  CAS  PubMed  Google Scholar 

  • Wang YH, Zhou FM (2017) Striatal but not extrastriatal dopamine receptors are critical to dopaminergic motor stimulation. Front Pharmacol 8:1–13

  • Wickens JR, Wilson CJ (1998) Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo. J Neurophysiol 79:2358–2364

    Article  CAS  PubMed  Google Scholar 

  • Wu JH, Corwin JV, Reep RL (2009) Organization of the corticostriatal projection from rat medial agranular cortex to far dorsolateral striatum. Brain Res 1280:69–76

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank MVZ Hugo Lecona Butrón for the support with the housing, care, maintenance, and monitoring the health of the experimental animals in the INR-LGII. We thank MVZ Javier Pérez Gallaga and M en C René Valdez Mijares for technical support.

Funding

This work was supported by INR-LGII, CONACyT (grant 288512 to A. Avila-Luna).

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Authors and Affiliations

  1. Lab. Neurofisiología Química de la Discapacidad, División de Neurociencias, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, SSa, Calz. México-Xochimilco 289, Col. Arenal de Guadalupe, 14389, Mexico City, Mexico

    Arturo Gálvez-Rosas, Alberto Avila-Luna & Antonio Bueno-Nava

  2. Departamento de Genética y Medicina Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, SSa, Calz. México-Xochimilco 289, Col. Arenal de Guadalupe, 14389, Mexico City, Mexico

    Margarita Valdés-Flores

  3. Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, SSa, Insurgentes Sur 3877, 14269, Mexico City, Mexico

    Sergio Montes

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  1. Arturo Gálvez-Rosas
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  2. Alberto Avila-Luna
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  3. Margarita Valdés-Flores
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  4. Sergio Montes
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  5. Antonio Bueno-Nava
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Correspondence to Antonio Bueno-Nava.

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Gálvez-Rosas, A., Avila-Luna, A., Valdés-Flores, M. et al. GABAergic imbalance is normalized by dopamine D1 receptor activation in the striatum contralateral to the cortical injury in motor deficit-recovered rats. Psychopharmacology 236, 2211–2222 (2019). https://doi.org/10.1007/s00213-019-05215-1

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