Behavioral changes are not directly related to striatal monoamine levels, number of nigral neurons, or dose of parkinsonian toxin MPTP in mice.
Behavioral analyses of mice intoxicated by the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) have generated conflicting results. We therefore analyzed the relationship between behavioral changes, loss of monoamine levels, and loss of dopaminergic cell bodies in groups of mice intoxicated with acute or subchronic MPTP protocols. Despite a higher degree of neuronal loss in the mice intoxicated using subchronic protocols, dopamine loss was severe and homogeneous in the striatum in all groups. Dopamine levels were less severely reduced in the frontal cortex in the three groups of MPTP-intoxicated mice. Norepinephrine and serotonin levels in the striatum were decreased only in the mice intoxicated with the acute protocol. The most surprising result was that the mice intoxicated with the subchronic protocols were more active than the saline-treated mice. As reported in rats with dopamine depletion in the prefrontal cortex, the hyperactivity observed in our mice could be due to the reduced dopamine levels detected in this structure.
INSERM U289, Experimental Neurology and Therapeutics, Hôpital de la Salpêtrière, 75013 Paris, France.
Estelle
E
Rousselet
Chantal
C
Joubert
Jacques
J
Callebert
Karine
K
Parain
Léon
L
Tremblay
Gaël
G
Orieux
Jean-Marie
JM
Launay
Charles
C
Cohen-Salmon
Etienne C
EC
Hirsch
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D015306:Biogenic Monoamines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine