Most antipsychotic (AP) drugs are dopamine (DA) D2 receptor (DRD2) antagonists and remain the main pharmacological treatment of schizophrenia. Long-term AP use can give rise to tardive dyskinesia. It has been reported that chronic treatment with APs induces DRD2 upregulation and oxidative stress, which have been associated with tardive dyskinesia. We showed previously that H₂O₂-induced oxidative stress increased DRD2 expression in human SH-SY5Y neuroblastoma cells. We report here the effects of AP drugs on DRD2 expression levels in the same cell line and the effects of the inhibition of oxidative phenomena by (±)-α-lipoic acid treatment. Haloperidol, a first-generation AP, induced an increase in DRD2 protein and mRNA levels, whereas amisulpride, a second-generation AP, had no significant effect. (±)-α-Lipoic acid pretreatment reversed the haloperidol-induced DRD2 upregulation in mRNA and protein levels. Furthermore, haloperidol induced a larger increase of oxidative stress biomarkers (protein carbonylation, lipid peroxidation, and superoxide anion production) than amisulpride. (±)-α-Lipoic acid also attenuated AP-induced oxidative stress. Inhibition of catecholamine synthesis by α-methyl-DL-tyrosine (AMPT) increased DRD2 expression and prevented further increase by APs. Our results suggest that haloperidol-induced DRD2 upregulation is linked to oxidative stress and provide potential mechanisms by which (±)-α-lipoic acid can be considered as a therapeutic agent to prevent and treat side effects related to the use of first-generation APs.
%0 Journal Article
%1 deslauriers_antipsychotic-induced_2011
%A Deslauriers, Jessica
%A Lefrançois, Marilou
%A Larouche, Annie
%A Sarret, Philippe
%A Grignon, Sylvain
%D 2011
%J Synapse (New York, N.Y.)
%K imported
%N 4
%P 321--331
%R 10.1002/syn.20851
%T Antipsychotic-induced DRD2 upregulation and its prevention by α-lipoic acid in SH-SY5Y neuroblastoma cells
%U http://www.ncbi.nlm.nih.gov/pubmed/20730801
%V 65
%X Most antipsychotic (AP) drugs are dopamine (DA) D2 receptor (DRD2) antagonists and remain the main pharmacological treatment of schizophrenia. Long-term AP use can give rise to tardive dyskinesia. It has been reported that chronic treatment with APs induces DRD2 upregulation and oxidative stress, which have been associated with tardive dyskinesia. We showed previously that H₂O₂-induced oxidative stress increased DRD2 expression in human SH-SY5Y neuroblastoma cells. We report here the effects of AP drugs on DRD2 expression levels in the same cell line and the effects of the inhibition of oxidative phenomena by (±)-α-lipoic acid treatment. Haloperidol, a first-generation AP, induced an increase in DRD2 protein and mRNA levels, whereas amisulpride, a second-generation AP, had no significant effect. (±)-α-Lipoic acid pretreatment reversed the haloperidol-induced DRD2 upregulation in mRNA and protein levels. Furthermore, haloperidol induced a larger increase of oxidative stress biomarkers (protein carbonylation, lipid peroxidation, and superoxide anion production) than amisulpride. (±)-α-Lipoic acid also attenuated AP-induced oxidative stress. Inhibition of catecholamine synthesis by α-methyl-DL-tyrosine (AMPT) increased DRD2 expression and prevented further increase by APs. Our results suggest that haloperidol-induced DRD2 upregulation is linked to oxidative stress and provide potential mechanisms by which (±)-α-lipoic acid can be considered as a therapeutic agent to prevent and treat side effects related to the use of first-generation APs.
@article{deslauriers_antipsychotic-induced_2011,
abstract = {Most antipsychotic {(AP)} drugs are dopamine {(DA)} D2 receptor {(DRD2)} antagonists and remain the main pharmacological treatment of schizophrenia. Long-term {AP} use can give rise to tardive dyskinesia. It has been reported that chronic treatment with {APs} induces {DRD2} upregulation and oxidative stress, which have been associated with tardive dyskinesia. We showed previously that {H₂O₂-induced} oxidative stress increased {DRD2} expression in human {SH-SY5Y} neuroblastoma cells. We report here the effects of {AP} drugs on {DRD2} expression levels in the same cell line and the effects of the inhibition of oxidative phenomena by (±)-α-lipoic acid treatment. Haloperidol, a first-generation {AP}, induced an increase in {DRD2} protein and {mRNA} levels, whereas amisulpride, a second-generation {AP}, had no significant effect. {(±)-α-Lipoic} acid pretreatment reversed the haloperidol-induced {DRD2} upregulation in {mRNA} and protein levels. Furthermore, haloperidol induced a larger increase of oxidative stress biomarkers (protein carbonylation, lipid peroxidation, and superoxide anion production) than amisulpride. {(±)-α-Lipoic} acid also attenuated {AP-induced} oxidative stress. Inhibition of catecholamine synthesis by {α-methyl-DL-tyrosine} {(AMPT)} increased {DRD2} expression and prevented further increase by {APs.} Our results suggest that haloperidol-induced {DRD2} upregulation is linked to oxidative stress and provide potential mechanisms by which (±)-α-lipoic acid can be considered as a therapeutic agent to prevent and treat side effects related to the use of first-generation {APs.}},
added-at = {2011-08-03T17:38:07.000+0200},
author = {Deslauriers, Jessica and Lefrançois, Marilou and Larouche, Annie and Sarret, Philippe and Grignon, Sylvain},
biburl = {https://www.bibsonomy.org/bibtex/2ccfd41b479a0b3ae94ae2eeaa18cddf6/crc_chus},
doi = {10.1002/syn.20851},
interhash = {4b0975768750bf3e98801db1c2e58734},
intrahash = {ccfd41b479a0b3ae94ae2eeaa18cddf6},
issn = {1098-2396},
journal = {Synapse {(New} York, {N.Y.)}},
keywords = {imported},
month = apr,
note = {{PMID:} 20730801},
number = 4,
pages = {321--331},
timestamp = {2011-08-03T20:51:55.000+0200},
title = {Antipsychotic-induced {DRD2} upregulation and its prevention by α-lipoic acid in {SH-SY5Y} neuroblastoma cells},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20730801},
volume = 65,
year = 2011
}