Vicente-Rodríguez, M; Rojo Gonzalez, L; Gramage, E; Fernández-Calle, R; Chen, Y; Pérez-García, C; Ferrer-Alcón, M; Uribarri, M; Bailey, A; Herradón, G
(2016)
Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation.
European Neuropsychopharmacology, 26 (11).
pp. 1794-1805.
ISSN 1873-7862
https://doi.org/10.1016/j.euroneuro.2016.09.002
SGUL Authors: Bailey, Alexis
|
PDF
Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (646kB) | Preview |
Abstract
It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice. Given the known contribution of D1 and D2 dopamine receptors to the neurotoxic effects of amphetamine, we also performed quantitative receptor autoradiography of both receptors in the brains of PTN-Tg and WT mice. D1 and D2 receptors binding in the striatum and other regions of interest was not altered by genotype or treatment. Finally, we found that amphetamine CPP was significantly reduced in PTN-Tg mice. The data demonstrate that PTN overexpression in the brain blocks the conditioning effects of amphetamine and enhances the characteristic striatal dopaminergic denervation caused by this drug. These results indicate for the first time deleterious effects of PTN in vivo by mechanisms that are probably independent of changes in the expression of D1 and D2 dopamine receptors. The data also suggest that PTN-induced neuroinflammation could be involved in the enhanced neurotoxic effects of amphetamine in the striatum of PTN-Tg mice.
Item Type: | Article | ||||||
---|---|---|---|---|---|---|---|
Additional Information: | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | ||||||
Keywords: | Astrogliosis, Inflammation, Methamphetamine, Midkine, Pleiotrophin, Reward, Psychiatry, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences | ||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
||||||
Journal or Publication Title: | European Neuropsychopharmacology | ||||||
ISSN: | 1873-7862 | ||||||
Language: | ENG | ||||||
Publisher License: | Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0 | ||||||
Projects: |
|
||||||
PubMed ID: | 27642078 | ||||||
Go to PubMed abstract | |||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108247 | ||||||
Publisher's version: | https://doi.org/10.1016/j.euroneuro.2016.09.002 |
Statistics
Actions (login required)
![]() |
Edit Item |