Morphological features of the ventral tegmental area: a brainstem structure related to attention deficit hyperactivity disorder

Year 2019, Volume: 13 Issue: 1, 66 - 70, 29.04.2019

Ayşegül Güngör Aydın Esat Adıgüzel

Abstract

Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder of the childhood and more interest
is raised by clinical investigators nowadays. In spite of being the most studied neurobehavioral condition in child psychiatry,
the pathophysiology of ADHD remains elusive. The ventral tegmental area (VTA) has been implicated in the etiology of
ADHD. This part of the midbrain needs to be investigated further due to its complex cytoarchitecture and connectivity in
order to gain insight into the neurobiology of ADHD. In this review, we will first briefly explain the history of the VTA
researches and then summarize the anatomical features and connectivity of this region. 

Keywords

attention deficit hyperactivity disorder; dopamine; mesocortical pathway; ventral tegmental area

References

• 1. Schultz W. Dopamine neurons and their role in reward mechanisms. Curr Opin Neurobiol 1997;7:191–7. 2. Matthews M, Nigg JT, Fair DA. Attention deficit hyperactivity disorder. Curr Top Behav Neurosci 2014;16:235–66. 3. Ikemoto S, Panksepp J. The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res Rev 1999;31:6–41. 4. Faraone SV, Biederman J. Neurobiology of attention-deficit hyperactivity disorder. Biol Psychiatry 1998;44:951–8. 5. Pliszka SR. The neuropsychopharmacology of attentiondeficit/ hyperactivity disorder. Biol Psychiatry 2005;57:1385–90. 6. Curatolo P, D'Agati E, Moavero R. The neurobiological basis of ADHD. Ital J Pediatr 2010;36:79. 7. Blum K, Chen ALC, Braverman ER, Comings DE, Chen TJH, Arcuri V, Blum SH, Downs BW, Waite RL, Notaro A, Lubar J, Williams L, Prihoda TJ, Palomo T, Oscar-Berman M. 2017 Attention-deficit-hyperactivity disorder and reward deficiency syndrome. Neuropsychiatr Dis Treat 2008;4:893–918. 8. Sesack SR, Grace AA. Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology 2010;35:27–47. 9. Malenka RC, Nestler EJ, Hyman SE. Molecular neuropharmacology: A foundation for clinical neuroscience. New York, NY: McGraw- Hill Medical; 2009. p. 516. 10. Swanson LW. The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 1982;9:321–53. 11. Margolis EB, Hjelmstad GO, Bonci A, Fields HL. Kappa-opioid agonists directly inhibit midbrain dopaminergic neurons. J Neurosci 2003;23:9981–6. 12. Margolis EB, Lock H, Hjelmstad GO, Fields HL. The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? J Physiol 2006;577:907–24. 13. Lammel S, Hetzel A, Häckel O, Jones I, Liss B, Roeper J. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron 2008;57:760–73. 14. Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K, Schwarz L, Gao XJ, Kremer EJ, Malenka RC, Luo L. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell 2015;162:622–34. 15. Faull RLM, Taylor DW, Carman JB. Soemmerring and the substantia nigra. Medical History 1968;12:297–9. 16. 16-Stevens JR. An anatomy of schizophrenia? Arch Gen Psychiatry 1973;29:177–89. 17. van Domburg PHMF, ten Donkelaar HI. The human substantia nigra and ventral tegmental area. A neuroanatomical study with notes on aging and aging diseases. Adv Anat Embryol Cell Biol 1991;121:1–32. 18. Ljungdahl A, Hökfelt T, Goldstein M, Park D. Retrograde peroxidase tracing of neurons combined with transmitter histochemistry. Brain Res 1975;84:313–9. 19. Björklund, A, Lindvall O. Dopamine containing systems in the CNS. In: Björklund A, Hökfelt T, editors. Handbook of chemical neuroanatomy. Vol. 2. Classical transmitters in the CNS, Part 1. Amsterdam: Elsevier; 1984. p. 55–122. 20. Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s; disease. Brain 1999;122:1437–48. 21. Lewis DA, Sesack SR. Dopamine systems in the primate brain. In: Bloom FE, Björklund A, Hökfelt T, editors. Handbook of chemical neuroanatomy. Vol. 13. Amsterdam: Elsevier; 1997. p. 263–375. 22. Kalivas PW, Nakamura M. Neural systems for behavioral activation and reward. Curr Opin Neurobiol 1999;9:223–7. 23. Halliday GM, Törk J. Comparative anatomy of the ventromedial mesencephalic tegmentum in the rat, cat, monkey and human. J Comp Neurol 1986;252:423–45. 24. Tsai C. The optic tracts and centers of the opossum. Didelphis virginiana. J Comp Neurol 1925; 39:173–216. 25. Phillipson, OT. The cytoarchitecture of the interfascicular nucleus and ventral tegmental area of Tsai in the rat. J Comp Neurol 1979a;187:85–98. 26. Phillipson, OT. A Golgi study of the ventral tegmental area of Tsai and interfascicular nucleus in the rat. J Comp Neurol 1979b;187:99– 116. 27. Paxinos G, Huang XF. Atlas of the human brainstem. San Diego, CA: Academic Press; 1995.28. Falck B, Hillarp NA, Thieme G, Torp A. Fluorescence of catechol amines and related compounds condensed with formaldehyde. Brain Res Bull 1982;9:11–5. 29. Carlsson A, Falck B, Hillarp NA. Cellular localization of brain monoamines. Acta Physiol Scand Suppl 1962;56:1–28. 30. Dahlström A, Fuxe K. Evidence for the existence of monoaminecontaining neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl 1964;232:1–55. 31. Oades RD, Halliday GM. Ventral tegmental (AlO) system: neurobiology. 1. Anatomy and connectivity. Brain Res 1987;434:117–65. 32. Bentivoglio M, Morelli M. The organisation and circuits of mesencephalic dopaminergic neurons and the distribution of dopamine receptors in the brain. In: Dunnett SB, Bentivoglio, Björklund A, Hökfelt T, editors. Handbook of chemical neuroanatomy (Dopamine). Vol. 21. London: Elsevier; 2005. p. 1–109. 33. Albanese A, Bentivoglio M. The organization of dopaminergic and non-dopaminergic mesencephalocortical neurons in the rat. Brain Res 1982;238:421–5. 34. Williams SM, Goldman-Rakic PS. Widespread origin of the primate mesofrontal dopamine system. Cereb Cortex 1998;8:321–45. 35. Lewis DA, Sesack SR, Levey AI, Rosenberg DR. Dopamine axons in primate prefrontal cortex: specificity of distribution, synaptic targets, and development. Adv Pharmacol 1998;42:703–6. 36. Engert V, Pruessner JC. Dopaminergic and noradrenergic contributions to functionality in ADHD: the role of methylphenidate. Curr Neuropharmacol 2008;6:322–8. 37. Volkow ND, Wang GJ, Fowler JS, Ding YS. Imaging the effects of methylphenidate on brain dopamine: new model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biol Psychiatry 2005;57:1410–5. 38. Ikemoto S, Murphy JM, McBride WJ. Self-infusion of GABA(A) antagonists directly into the ventral tegmental area and adjacent regions. Behav Neurosci 1997;111:369–80. 39. Bolanos CA, Neve RL, Nestler EJ. Phospholipase C gamma in distinct regions of the ventral tegmental area differentially regulates morphine-induced locomotor activity. Synapse 2005;56:166–9. 40. Tan Y, Brog JS, Williams ES, Zahm DS. Morphometric analysis of ventral mesencephalic neurons retrogradely labeled with fluoro-gold following injections in the shell, core and rostral pole of the rat nucleus accumbens. Brain Res 1995;689:151–6. 41. Margolis EB, Mitchell JM, Ishikawa J, Hjelmstad GO, Fields HL. Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition. J Neurosci 2008;28:8908–13. 42. Lammel S, Ion DI, Roeper J, Malenka RC. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron 2011;70:855–62. 43. Sesack SR, Hawrylak VA, Matus C, Guido MA, Levey AI. Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J Neurosci 1998;18:2697–708. 44. Lewis DA, Melchitzky DS, Sesack SR, Whitehead RE, Auh S, Sampson A. Dopamine transporter immunoreactivity in monkey cerebral cortex: regional, laminar, and ultrastructural localization. J Comp Neurol 2001;432:119–36. 45. Moghaddam B, Berridge CW, Goldman-Rakic PS, Bunney BS, Roth RH. In vivo assessment of basal and drug-induced dopamine release in cortical and subcortical regions of the anesthetized primate. Synapse 1993;13:215–22. 46. Garris PA, Collins LB, Jones SR, Wightman RM. Evoked extracellular dopamine in vivo in the medial prefrontal cortex. J Neurochem 1993;61:637–47.