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Effects of chronic antipsychotic treatment on dopamine synthesis

Conference Paper


Abstract


  • Purpose: The mesolimbic dopamine (DA) pathway, with projections from

    the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc),

    is involved in antipsychotic drug (APD) treatment for schizophrenia

    symptoms. Whilst APD mechanisms of action have been thought through

    DA D2-receptor antagonism, recent developments of D2 partial-agonist

    APDs has thrown to light the potential of controlling DA synthesis.

    This study aimed to investigate the effects of APDs Haloperidol (a D2

    antagonist) and Aripiprazole (a D2 partial agonist), on DA synthesis

    markers in the mesolimbic DA-pathway. Methods: Male Sprague-Dawley

    rats (n=6/group) were administered orally with Aripiprazole (0.75mg/kg,

    t.i.d.), Haloperidol (0.1mg/kg, t.i.d.), or vehicle (control) for 10-weeks.

    Levels of Phospho-Tyrosine Hydroxylase (p-TH), Tyrosine Hydroxylase

    (TH), and Dopamine Transporter (DAT) was determined by Western blot,

    whilst DOPA and DA levels were measured by Gas Chromatography-

    Mass Spectrometry. Results: In the VTA, Aripiprazole and Haloperidol

    decreased p-TH and TH expression. In the NAc, both treatments

    decreased TH expression (both p<0.01). In addition, Aripiprazole lowered

    DA levels (p<0.05), and Haloperidol treatment decreased DOPA levels

    (p<0.05) compared with controls. Haloperidol significantly increased

    DAT level in the NAc (p<0.05). Conclusion: Although both Aripiprazole

    and Haloperidol have well documented mechanisms of action on DA

    receptors to provide their therapeutic efficacy, this study revealed that

    they also have significant effects on DA synthesis in the mesolimbic

    pathway and in turn a low DA availability in the synapse. Future studies

    into the pharmacology of APDs may look into their exact mechanisms

    of action on the regulation of DA synthesis; potentially providing further

    knowledge behind Aripiprazoles therapeutic efficacy and future potential

    APD development.

Authors


Publication Date


  • 2013

Citation


  • De Santis, M., Huang, X. -F., Jenner, A. & Deng, C. (2013). Effects of chronic antipsychotic treatment on dopamine synthesis. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 115-115). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/902

Start Page


  • 115

End Page


  • 115

Place Of Publication


  • Australia

Abstract


  • Purpose: The mesolimbic dopamine (DA) pathway, with projections from

    the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc),

    is involved in antipsychotic drug (APD) treatment for schizophrenia

    symptoms. Whilst APD mechanisms of action have been thought through

    DA D2-receptor antagonism, recent developments of D2 partial-agonist

    APDs has thrown to light the potential of controlling DA synthesis.

    This study aimed to investigate the effects of APDs Haloperidol (a D2

    antagonist) and Aripiprazole (a D2 partial agonist), on DA synthesis

    markers in the mesolimbic DA-pathway. Methods: Male Sprague-Dawley

    rats (n=6/group) were administered orally with Aripiprazole (0.75mg/kg,

    t.i.d.), Haloperidol (0.1mg/kg, t.i.d.), or vehicle (control) for 10-weeks.

    Levels of Phospho-Tyrosine Hydroxylase (p-TH), Tyrosine Hydroxylase

    (TH), and Dopamine Transporter (DAT) was determined by Western blot,

    whilst DOPA and DA levels were measured by Gas Chromatography-

    Mass Spectrometry. Results: In the VTA, Aripiprazole and Haloperidol

    decreased p-TH and TH expression. In the NAc, both treatments

    decreased TH expression (both p<0.01). In addition, Aripiprazole lowered

    DA levels (p<0.05), and Haloperidol treatment decreased DOPA levels

    (p<0.05) compared with controls. Haloperidol significantly increased

    DAT level in the NAc (p<0.05). Conclusion: Although both Aripiprazole

    and Haloperidol have well documented mechanisms of action on DA

    receptors to provide their therapeutic efficacy, this study revealed that

    they also have significant effects on DA synthesis in the mesolimbic

    pathway and in turn a low DA availability in the synapse. Future studies

    into the pharmacology of APDs may look into their exact mechanisms

    of action on the regulation of DA synthesis; potentially providing further

    knowledge behind Aripiprazoles therapeutic efficacy and future potential

    APD development.

Authors


Publication Date


  • 2013

Citation


  • De Santis, M., Huang, X. -F., Jenner, A. & Deng, C. (2013). Effects of chronic antipsychotic treatment on dopamine synthesis. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 115-115). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/902

Start Page


  • 115

End Page


  • 115

Place Of Publication


  • Australia