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Dampened Amphetamine-Stimulated Behavior and Altered Dopamine Transporter Function in the Absence of Brain GDNF
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
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2017 (Engelska)Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 37, nr 6, s. 1581-1590Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction and Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in various disorders with disturbed dopamine homeostasis. However, the outcomes from preclinical and clinical studies vary, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function. Nevertheless, the current lack of appropriate animal models has limited this understanding. Therefore, we have generated novel mouse models to study conditional Gdnf deletion in the CNS during embryonic development and reduction of striatal GDNF levels in adult mice via AAV-Cre delivery. We found that both of these mice have reduced amphetamine-induced locomotor response and striatal dopamine efflux. Embryonic GDNF deletion in the CNS did not affect striatal dopamine levels or dopamine release, but dopamine reuptake was increased due to increased levels of both total and synaptic membrane-associated dopamine transporters. Collectively, these results suggest that endogenous GDNF plays an important role in regulating the function of dopamine transporters in the striatum.

Ort, förlag, år, upplaga, sidor
2017. Vol. 37, nr 6, s. 1581-1590
Nyckelord [en]
amphetamine, cyclic voltammetry, dopamine, dopamine transporter, GDNF, striatum
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-132628DOI: 10.1523/JNEUROSCI.1673-16.2016ISI: 000393572400017PubMedID: 28096470OAI: oai:DiVA.org:umu-132628DiVA, id: diva2:1085708
Tillgänglig från: 2017-03-30 Skapad: 2017-03-30 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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