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D1 Antagonists and D2 Agonists Have Opposite Effects on the Metabolism of Dopamine in the Rat Striatum

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Abstract

The striatum is known to possess high levels of D1-like and D2-like receptors (D1Rs and D2Rs, respectively). We have previously shown that selective inhibition of D1Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D2Rs by endogenous dopamine (DA). Here, we examined whether activation of D2Rs modulates the metabolism and synthesis of DA in the striatum. We used male Wistar rats to evaluate the effects of the systemic administration of a D2R agonist (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these compounds with pargyline on the inhibition of monoamine oxidase. DA and l-3,4-dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-l-phenylalanine (l-DOPA) content were measured using high performance liquid chromatography. The systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg, significantly (P < 0.05) increased DOPAC levels and the DOPAC/DA ratio. At 2, 4 and 8 mg/kg, the administration of bromocriptine alone significantly (P < 0.05) decreased DOPAC levels, l-DOPA content and the DOPAC/DA ratio, whereas at 2 mg/kg, it decreased DA levels. In both groups, co-administration of either SCH-23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA ratio by approximately 70 % compared to the levels observed in the control groups. In conclusion, administration of the D2R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D1R antagonist SCH-23390 induced the opposite effects.

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References

  1. Kreitzer AC, Malenka RC (2008) Striatal plasticity and basal ganglia circuit function. Neuron 60(4):543–554

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. O’Neill C, Evers-Donnelly A, Nicholson D, O’Boyle KM, O’Connor JJ (2009) D-2 receptor-mediated inhibition of dopamine release in the rat striatum in vitro is modulated by CB1 receptors: studies using fast cyclic voltammetry. J Neurochem 108(3):545–551

    Article  PubMed  Google Scholar 

  3. 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(6201):783–787

    Article  CAS  PubMed  Google Scholar 

  4. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78(1):189–225

    CAS  PubMed  Google Scholar 

  5. 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(6319):614–619

    Article  CAS  PubMed  Google Scholar 

  6. 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(6319):610–614

    Article  PubMed  Google Scholar 

  7. Cubeddu LX, Hoffmann IS (1982) Operational characteristics of the inhibitory feedback mechanism for regulation of dopamine release via presynaptic receptors. J Pharmacol Exp Ther 223(2):497–501

    CAS  PubMed  Google Scholar 

  8. Schmitz Y, Schmauss C, Sulzer D (2002) Altered dopamine release and uptake kinetics in mice lacking D2 receptors. J Neurosci 22(18):8002–8009

    CAS  PubMed  Google Scholar 

  9. 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(5):228–235

    Article  CAS  PubMed  Google Scholar 

  10. Bolam JP, Hanley JJ, Booth PA, Bevan MD (2000) Synaptic organisation of the basal ganglia. J Anat 196(Pt 4):527–542

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Koos T, Tepper JM (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2(5):467–472

    Article  CAS  PubMed  Google Scholar 

  12. Mallet N, Le Moine C, Charpier S, Gonon F (2005) Feedforward inhibition of projection neurons by fast-spiking GABA interneurons in the rat striatum in vivo. J Neurosci 25(15):3857–3869

    Article  CAS  PubMed  Google Scholar 

  13. Imperato A, Di Chiara G (1988) Effects of locally applied D-1 and D-2 receptor agonists and antagonists studied with brain dialysis. Eur J Pharmacol 156(3):385–393

    Article  CAS  PubMed  Google Scholar 

  14. Rahman S, McBride WJ (2001) D1–D2 dopamine receptor interaction within the nucleus accumbens mediates long-loop negative feedback to the ventral tegmental area (VTA). J Neurochem 77(5):1248–1255

    Article  CAS  PubMed  Google Scholar 

  15. Saklayen SS, Mabrouk OS, Pehek EA (2004) Negative feedback regulation of nigrostriatal dopamine release: mediation by striatal D1 receptors. J Pharmacol Exp Ther 311(1):342–348

    Article  CAS  PubMed  Google Scholar 

  16. Bueno-Nava A, Gonzalez-Pina R, Avila-Luna A, Alfaro-Rodriguez A (2011) Paradigm of negative feedback via long-loop in the striatal dopamine release modulation in the rat. Rev Neurol 52(6):371–377

    CAS  PubMed  Google Scholar 

  17. 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(8):1783–1789

    Article  CAS  PubMed  Google Scholar 

  18. Jaber M, Robinson SW, Missale C, Caron MG (1996) Dopamine receptors and brain function. Neuropharmacology 35(11):1503–1519

    Article  CAS  PubMed  Google Scholar 

  19. Beaulieu J-M, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63(1):182–217

    Article  CAS  PubMed  Google Scholar 

  20. Vallone D, Picetti R, Borrelli E (2000) Structure and function of dopamine receptors. Neurosci Biobehav Rev 24(1):125–132

    Article  CAS  PubMed  Google Scholar 

  21. Takashima H, Tsujihata M, Kishikawa M, Freed WJ (1999) Bromocriptine protects dopaminergic neurons from levodopa-induced toxicity by stimulating D(2)receptors. Exp Neurol 159(1):98–104

    Article  CAS  PubMed  Google Scholar 

  22. Bonuccelli U, Del Dotto P, Rascol O (2009) Role of dopamine receptor agonists in the treatment of early Parkinson’s disease. Parkinsonism Relat Disord 15(Suppl 4):S44–S53

    Article  PubMed  Google Scholar 

  23. 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 

  24. Festing MF (1994) Reduction of animal use: experimental design and quality of experiments. Lab Anim 28(3):212–221

    Article  CAS  PubMed  Google Scholar 

  25. Harsing LGJ (2008) Dopamine and the dopaminergic systems of the brain: neurotransmitter systems. In: Lajtha A, Vizi ES (ed) Handbook of neurochemistry and molecular neurobiology, 3rd edn. Springer, New York, pp 149–170

    Chapter  Google Scholar 

  26. Alfaro-Rodriguez A, Alonso-Spilsbury M, Arch-Tirado E, Gonzalez-Pina R, Arias-Montano J-A, Bueno-Nava A (2013) Histamine H-3 receptor activation prevents dopamine D-1 receptor-mediated inhibition of dopamine release in the rat striatum: a microdialysis study. Neurosci Lett 552:5–9

    Article  CAS  PubMed  Google Scholar 

  27. Henry B, Crossman AR, Brotchie JM (1998) Characterization of enhanced behavioral responses to l-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. Exp Neurol 151(2):334–342

    Article  CAS  PubMed  Google Scholar 

  28. Prikhojan A, Brannan T, Yahr MD (2000) Comparative effects of repeated administration of dopamine agonists on circling behavior in rats. J Neural Transm (Vienna, Austria : 1996) 107(10):1159–1164

    Article  CAS  Google Scholar 

  29. Lindgren HS, Rylander D, Ohlin KE, Lundblad M, Cenci MA (2007) The “motor complication syndrome” in rats with 6-OHDA lesions treated chronically with l-DOPA: relation to dose and route of administration. Behav Brain Res 177(1):150–159

    Article  CAS  PubMed  Google Scholar 

  30. Lane EL, Dunnett SB (2010) Pre-treatment with dopamine agonists influence l-DOPA mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat. Behav Brain Res 213(1):66–72

    Article  CAS  PubMed  Google Scholar 

  31. Smolders I, De Klippel N, Sarre S, Ebinger G, Michotte Y (1995) Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat. Eur J Pharmacol 284(1–2):83–91

    Article  CAS  PubMed  Google Scholar 

  32. 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(1):177–181

    Article  CAS  PubMed  Google Scholar 

  33. Mura A, Jackson D, Manley MS, Young SJ, Groves PM (1995) Aromatic l-amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site for the conversion of exogenous l-DOPA to dopamine. Brain Res 704(1):51–60

    Article  CAS  PubMed  Google Scholar 

  34. Lloyd K, Hornykiewicz O (1970) Parkinson’s disease: activity of l-DOPA decarboxylase in discrete brain regions. Science (New York, NY) 170(3963):1212–1213

    Article  CAS  Google Scholar 

  35. Ogawa N, Tanaka K, Asanuma M (2000) Bromocriptine markedly suppresses levodopa-induced abnormal increase of dopamine turnover in the parkinsonian striatum. Neurochem Res 25(6):755–758

    Article  CAS  PubMed  Google Scholar 

  36. Fekete MI, Herman JP, Kanyicska B, Palkovits M (1979) Dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) levels of individual brain nuclei, effects of haloperidol and pargyline. J Neural Transm 45(3):207–218

    Article  CAS  PubMed  Google Scholar 

  37. Berry MD (2011) The effects of pargyline and 2-phenylethylamine on D1-like dopamine receptor binding. J Neural Transm 118(7):1115–1118

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Dr. Ivonne M. Heuze de Icasa and Dr. Emilio E. Quintana for support with the experimental animals. We thank MVZ. Hugo Lecona Butrón for support with the housing, care, maintenance and monitoring of the health of the experimental animals.

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Authors and Affiliations

  1. División de Neurociencias, Instituto Nacional de Rehabilitación, ‘Luis Guillermo Ibarra Ibarra’, Secretaría de Salud, Calzada México-Xochimilco 289, Arenal de Guadalupe, C.P. 14389, Mexico City, Mexico

    Alberto Avila-Luna, Jacqueline Prieto-Leyva, Arturo Gálvez-Rosas, Alfonso Alfaro-Rodriguez, Rigoberto Gonzalez-Pina & Antonio Bueno-Nava

  2. Lab. de Neurofisiología Química de la Discapacidad-División de Neurociencias, Instituto Nacional de Rehabilitación-LGII, Calz. México-Xochimilco 289, Col. Arenal de Guadalupe, Deleg. Tlalpan, C.P. 14383, Mexico City, Mexico

    Antonio Bueno-Nava

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  1. Alberto Avila-Luna
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  2. Jacqueline Prieto-Leyva
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  3. Arturo Gálvez-Rosas
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  4. Alfonso Alfaro-Rodriguez
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  5. Rigoberto Gonzalez-Pina
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  6. Antonio Bueno-Nava
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Correspondence to Antonio Bueno-Nava.

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Avila-Luna, A., Prieto-Leyva, J., Gálvez-Rosas, A. et al. D1 Antagonists and D2 Agonists Have Opposite Effects on the Metabolism of Dopamine in the Rat Striatum. Neurochem Res 40, 1431–1437 (2015). https://doi.org/10.1007/s11064-015-1611-4

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  • DOI: https://doi.org/10.1007/s11064-015-1611-4

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