title: Forebrain dopamine depletion impairs motor behavior in lamprey.
abstract: The structure of the basal ganglia appears to be conserved throughout vertebrate evolution, with characteristic cellular and transmitter components in each area, and the same types of afferent input. As described in rodents and primates, depletion of the striatal dopamine results in characteristic motor deficits. To explore if this role of the basal ganglia in modulating motor function was present early in vertebrate evolution, we investigated here the effects of striatal dopamine depletion in the lamprey, a cyclostome, which diverged from the main vertebrate line around 560 million years ago. The lamprey striatum contains the same cellular elements as found in mammals, and receives the same types of input, including a prominent dopamine innervation. We show here that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 100 mg/kg i.p.), a neurotoxin, depletes forebrain and striatal dopamine levels in lamprey to 15% of control values, and has profound effects on motor performance. Twenty-four and 48 h after MPTP injection, lampreys demonstrated marked reductions in spontaneous swimming and the duration of each swimming episode. Impairments in the ability to initiate movements were shown by a decreased rate of initiation. Furthermore, the initiation and maintenance of locomotion induced by olfactory mucosa stimulation was severely impaired, as was the coordination of different motor tasks. These deficits were ameliorated by the dopamine agonist apomorphine. The motor deficits arising after striatal dopamine depletion are thus qualitatively similar in cyclostomes and mammals. The role of the dopamine innervation of the striatum thus appears to be conserved throughout vertebrate evolution.
authors.affiliation: Nobel institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, SE 17177, Sweden.
authors.forename: R H
authors.initials: RH
authors.lastname: Thompson
authors.forename: A
authors.initials: A
authors.lastname: Ménard
authors.forename: M
authors.initials: M
authors.lastname: Pombal
authors.forename: S
authors.initials: S
authors.lastname: Grillner
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D004298:Dopamine / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology; D018492:Dopamine Antagonists / Q000008:administration & dosage; D007798:Lampreys / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology*; D013550:Swimming / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine