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Chronic antipsychotic treatment differentially modulates protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways, N-methyl-D-aspartate receptor and γ-aminobutyric acid A receptors in nucleus accumbens of juvenile rats

Journal Article


Abstract


  • Background: Antipsychotics are developed to treat mental disorders in adults; however, the prescription (mostly “off-label”) of antipsychotics for children/adolescents has been constantly increasing over years. The influences of antipsychotics on juveniles requires investigation to validate their clinic use. Antipsychotics mainly exert their effects via several receptors and signaling pathways.

    Aims: This study examined the effects of aripiprazole, olanzapine, and risperidone on selected signaling pathways, N-methyl-D-aspartate, and γ-aminobutyric acid A receptors in juveniles.

    Methods: Rats were orally administered aripiprazole (1 mg/kg), olanzapine (1 mg/kg), risperidone (0.3 mg/kg), or vehicle three times/day from postnatal day 23 (±1 day) for three weeks. The effects of antipsychotics in the nucleus accumbens and caudate putamen were measured by Western blots.

    Results: In the nucleus accumbens, all three drugs differentially increased N-methyl-D-aspartate and γ-aminobutyric acid A receptor expression. Additionally, all three antipsychotics differentially elevated the phosphorylation of glycogen synthase kinase 3 beta, β-catenin, and cAMP-responsive element-binding protein 1. In the caudate putamen, olanzapine increased β-catenin phosphorylation; and aripiprazole and olanzapine elevated γ-aminobutyric acid A receptor levels. Correlation analysis indicated that antipsychotics might modulate N-methyl-D-aspartate receptors via glycogen synthase kinase 3 beta-β-catenin signaling and/or cAMP-responsive element-binding protein 1 activation.

    Conclusions: These findings suggest that antipsychotics can affect protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways in juveniles; and their modulation on N-methyl-D-aspartate and γ-aminobutyric acid A receptors is probably through glycogen synthase kinase 3 beta-β-catenin signaling and/or cAMP-responsive element-binding protein 1 activation.

Publication Date


  • 2018

Citation


  • Pan, B., Lian, J. & Deng, C. (2018). Chronic antipsychotic treatment differentially modulates protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways, N-methyl-D-aspartate receptor and γ-aminobutyric acid A receptors in nucleus accumbens of juvenile rats. Journal of Psychopharmacology, 32 (11), 1252-1263.

Scopus Eid


  • 2-s2.0-85053332174

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1324

Number Of Pages


  • 11

Start Page


  • 1252

End Page


  • 1263

Volume


  • 32

Issue


  • 11

Place Of Publication


  • United Kingdom

Abstract


  • Background: Antipsychotics are developed to treat mental disorders in adults; however, the prescription (mostly “off-label”) of antipsychotics for children/adolescents has been constantly increasing over years. The influences of antipsychotics on juveniles requires investigation to validate their clinic use. Antipsychotics mainly exert their effects via several receptors and signaling pathways.

    Aims: This study examined the effects of aripiprazole, olanzapine, and risperidone on selected signaling pathways, N-methyl-D-aspartate, and γ-aminobutyric acid A receptors in juveniles.

    Methods: Rats were orally administered aripiprazole (1 mg/kg), olanzapine (1 mg/kg), risperidone (0.3 mg/kg), or vehicle three times/day from postnatal day 23 (±1 day) for three weeks. The effects of antipsychotics in the nucleus accumbens and caudate putamen were measured by Western blots.

    Results: In the nucleus accumbens, all three drugs differentially increased N-methyl-D-aspartate and γ-aminobutyric acid A receptor expression. Additionally, all three antipsychotics differentially elevated the phosphorylation of glycogen synthase kinase 3 beta, β-catenin, and cAMP-responsive element-binding protein 1. In the caudate putamen, olanzapine increased β-catenin phosphorylation; and aripiprazole and olanzapine elevated γ-aminobutyric acid A receptor levels. Correlation analysis indicated that antipsychotics might modulate N-methyl-D-aspartate receptors via glycogen synthase kinase 3 beta-β-catenin signaling and/or cAMP-responsive element-binding protein 1 activation.

    Conclusions: These findings suggest that antipsychotics can affect protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways in juveniles; and their modulation on N-methyl-D-aspartate and γ-aminobutyric acid A receptors is probably through glycogen synthase kinase 3 beta-β-catenin signaling and/or cAMP-responsive element-binding protein 1 activation.

Publication Date


  • 2018

Citation


  • Pan, B., Lian, J. & Deng, C. (2018). Chronic antipsychotic treatment differentially modulates protein kinase A- and glycogen synthase kinase 3 beta-dependent signaling pathways, N-methyl-D-aspartate receptor and γ-aminobutyric acid A receptors in nucleus accumbens of juvenile rats. Journal of Psychopharmacology, 32 (11), 1252-1263.

Scopus Eid


  • 2-s2.0-85053332174

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1324

Number Of Pages


  • 11

Start Page


  • 1252

End Page


  • 1263

Volume


  • 32

Issue


  • 11

Place Of Publication


  • United Kingdom