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Dopaminergic transmission in STOP null mice.
Philippe Brun1, Mélina Bégou, Annie Andrieux
1Institut Fédératif des Neurosciences de Lyon; UCBL, Faculté de Pharmacie, Laboratoire de Neuropharmacologie et Neurochimie, Lyon, France. pbrun@sante.univ-lyon1.fr
Journal of Neurochemistry
|June 15, 2005
Summary
STOP null mice exhibit increased dopamine transmission, leading to behavioral disorders. Neuroleptic treatment normalizes this hyper-dopaminergic activity, suggesting a link to schizophrenia.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Neuroleptics counteract hyper-dopaminergic transmission for antipsychotic effects.
- STOP null mice display neuroleptic-sensitive behavioral disorders.
- Microtubule-stabilizing proteins play a role in neurological function.
Purpose of the Study:
- To investigate the dopaminergic status in STOP null mice.
- To correlate behavioral phenotypes with dopamine transmission.
- To explore the neurobiological underpinnings of mental diseases.
Main Methods:
- Behavioral analysis of STOP null and wild-type mice.
- Measurement of dopamine efflux using quantitative microdialysis and electrochemical techniques.
- Pharmacological intervention with neuroleptics and amphetamine.
Main Results:
- STOP null mice exhibit hyper-locomotor activity and increased locomotor reactivity to amphetamine.
- Dopamine efflux is significantly increased in the nucleus accumbens of STOP null mice.
- Basal dopamine concentrations are normal, but dopamine release is elevated, with normal uptake and auto-inhibition.
Conclusions:
- STOP null mice present with limbic hyper-dopaminergy and hippocampal hypo-glutamatergy.
- These neurotransmission defects are associated with behavioral disorders.
- The findings suggest a potential link between STOP protein, dopamine dysregulation, and schizophrenia.