Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic.
Mice unable to synthesize dopamine (DA) specifically in dopaminergic neurons were created by inactivating the tyrosine hydroxylase (TH) gene then by restoring TH function in noradrenergic cells. These DA-deficient (DA-/-) mice were born at expected frequency but became hypoactive and stopped feeding a few weeks after birth. Midbrain dopaminergic neurons, their projections, and most characteristics of their target neurons in the striatum appeared normal. Within a few minutes of being injected with L-dihdroxyphenylalanine (L-DOPA), the product of TH, the DA-/- mice became more active and consumed more food than control mice. With continued administration of L-DOPA, nearly normal growth was achieved. These studies indicate that DA is essential for movement and feeding, but is not required for the development of neural circuits that control these behaviors.
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Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle 98195-7370, USA.
Palmiter
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D000320:Adrenergic Fibers / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D004298:Dopamine / Q000032:analysis / Q000172:deficiency*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004327:Drinking Behavior / Q000502:physiology*; D004399:Dynorphins / Q000096:biosynthesis; D004622:Embryo, Mammalian / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology; D008636:Mesencephalon / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D009638:Norepinephrine / Q000096:biosynthesis / Q000172:deficiency; D013373:Substance P / Q000096:biosynthesis; D019076:Transgenes / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D013373:Substance P; D007980:Levodopa; D004399:Dynorphins; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine