Post-pubertal emergence of alterations in locomotor activity in stop null mice.
Overt schizophrenia is preceded by a prodromal phase during which juvenile patients display attenuated schizophrenia-related symptoms. Here, we have looked for evidence of a prodromal phase in juvenile STOP null mice, which, during adulthood, imitate features of schizophrenia. We have principally examined locomotor activity, which is abnormal in adult STOP null mice, and its apparent relationship with perturbed glutamatergic and dopaminergic transmission. When compared to corresponding wild-type mice, juvenile STOP null mice did not exhibit the basal hyperlocomotion or locomotor hypersensitivity to mild stress observed in adult mice. Juvenile STOP null mice also lacked disturbed locomotor sensitivity to MK-801, which was evident in adult mice. In contrast, juvenile STOP null mice exhibited a similar hypersensitivity to amphetamine as that found in adult mice. Thus, STOP null mice exhibited both a progression of locomotor activity defects over time and subtle alterations in the prepubertal period. We suggest that the pattern of locomotor disturbances observed in this study is related to altered dopaminergic reactivity in juvenile mice without major disturbance in glutamatergic transmission, whereas both neurotransmitter systems are impaired in adult mice.
Bégou
Mélina
M
Institut Fédératif des Neurosciences de Lyon, Bron, France. melina.begou@u-clermont1.fr
Brun
Philippe
P
Bertrand
Jean-Baptiste
JB
Job
Didier
D
Schweitzer
Annie
A
D'Amato
Thierry
T
Saoud
Mohamed
M
Andrieux
Annie
A
Suaud-Chagny
Marie-Françoise
MF
D000375:Aging / Q000502:physiology*; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics*
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse; D016291:Dizocilpine Maleate; D000661:Amphetamine