A possible role for dopamine D 3 receptor stimulation in the induction of neurogenesis in the adult rat substantia nigra

Abstract

Small molecule neurotransmitters, such as dopamine, have been shown to regulate cell cycles in the developing brain [ Spencer GE, Klumperman J, Syed NI (1998) Neurotransmitters and neurodevelopment: Role of dopamine in neurite outgrowth, target selection and specific synapse formation. Perspect Dev Neurobiol 5:451–467; Ohtani N, Goto T, Waeber C, Bhide PG (2003) Dopamine modulates cell cycle in the lateral ganglionic eminence. J Neurosci 23:2840–2850] and may provide an alternative to traditional growth factors for the regulation of neurogenesis. Specifically, the dopamine D 3 receptor appears to play an important role in neural development, and shows a persistent expression through adulthood in the proliferative subventricular zone [Diaz J, Ridray S, Mignon V, Griffon N, Schwartz JC, Sokoloff P (1997) Selective expression of dopamine D 3 receptor mRNA in proliferative zones during embryonic development of the rat brain. J Neurosci 17:4282–4292]. Furthermore, pharmacological stimulation of D 3 receptors promotes proliferation of adult subventricular zone cells, both in vitro [Coronas V, Bantubungi K, Fombonne J, Krantic S, Schiffmann SN, Roger M (2004) Dopamine D 3 receptor stimulation promotes the proliferation of cells derived from the post-natal subventricular zone. J Neurochem 91:1292–1301] and in vivo [Van Kampen JM, Hagg T, Robertson HA (2004) Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D 3 receptor stimulation. Eur J Neurosci 19:2377–2387]. In earlier work, we have demonstrated the induction of cell proliferation in the subventricular zone of the adult rat brain accompanied by a dramatic 10-fold induction of neurogenesis in the neighboring neostriatum, following administration of the preferential D 3 receptor agonist, 7-hydroxy- N, N-di- n-propyl-2-aminotetralin [Van Kampen JM, Hagg T, Robertson HA (2004) Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D 3 receptor stimulation. Eur J Neurosci 19:2377–2387]. Dopamine D 3 receptors have also been found in the substantia nigra [Diaz J, Pilon C, Le Foll B, Gross C, Triller A, Schwartz JC, Sokoloff P (2000) Dopamine D 3 receptors expressed by all mesencephalic dopamine neurons. J Neurosci 20:8677–8684], a region of the adult brain shown to exhibit ongoing cytogenesis and neurogenic potential [Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW, Gage FH (2002) The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22:6639–6649; Zhao M, Momma S, Delfani K, Carlen M, Cassidy RM, Johansson CB, Brismar H, Shupliakov O, Frisen J, Janson AM (2003) Evidence for neurogenesis in the adult mammalian substantia nigra. Proc Natl Acad Sci U S A 100:7925–7930]. We have found that chronic intraventricular administration of 7-hydroxy- N, N-di- n-propyl-2-aminotetralin triggers a profound induction of cell proliferation in the rat substantia nigra and promotes the adoption of a neuronal phenotype in a proportion of these newly generated cells.