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Binding affinity of aripiprazole to the dopamine D2 receptor in different regions of the rat brain

Conference Paper


Abstract


  • Purpose: The new antipsychotic drug aripiprazole has a high affinity

    for the dopamine D2 receptor (D2R) and can treat multiple symptoms

    of schizophrenia with reduced risk of extrapyramidal side-effects (EPS).

    The question of how aripiprazole achieves its therapeutic benefits

    through the D2R, without causing EPS is currently unanswered. This

    study aimed to examine the binding affinity of aripiprazole to D2R in

    specific nuclei of the mesolimbic and nigrostriatal dopamine pathways,

    which are implicated in the therapeutic effects and EPS side effects of

    antipsychotic drugs, respectively. METHODS: Brain tissue obtained

    from male Sprague Dawley rats (n=7) was sectioned onto polysine slides

    and D2Rs were visualised by competition autoradiographic techniques

    using 20nM [3H]raclopride. D2R binding density was quantified in the

    ventral tegmental area (VTA) and nucleus accumbens (NAc) (mesolimbic

    pathway), substantia nigra (SN) and caudate putamen (CPU) (nigrostriatal

    pathway). The mean results of 7 animals were combined for each region

    of interest. RESULTS: Aripiprazole had a high affinity for the D2R in all

    regions examined. Aripiprazole had mean inhibition constants (Ki) of:

    15nM in the VTA, 71nM in the NAc, 21nM in the SN, 29nM in the CPU.

    CONCLUSION: Aripiprazole has a high binding affinity for the D2R in

    specific nuclei of the dopaminergic pathways in the rat brain. Aripiprazole

    affinity for D2Rs in the NAc was slightly lower than the other regions

    of interest; however values were similar in range, therefore differences

    in binding affinity cannot explain its reduced EPS. The mechanisms by

    which aripiprazole achieves its therapeutic effects, while avoiding EPS,

    require further investigation.

Publication Date


  • 2013

Citation


  • Weston-Green, K. & Deng, C. (2013). Binding affinity of aripiprazole to the dopamine D2 receptor in different regions of the rat brain. 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/903

Start Page


  • 115

End Page


  • 115

Place Of Publication


  • Australia

Abstract


  • Purpose: The new antipsychotic drug aripiprazole has a high affinity

    for the dopamine D2 receptor (D2R) and can treat multiple symptoms

    of schizophrenia with reduced risk of extrapyramidal side-effects (EPS).

    The question of how aripiprazole achieves its therapeutic benefits

    through the D2R, without causing EPS is currently unanswered. This

    study aimed to examine the binding affinity of aripiprazole to D2R in

    specific nuclei of the mesolimbic and nigrostriatal dopamine pathways,

    which are implicated in the therapeutic effects and EPS side effects of

    antipsychotic drugs, respectively. METHODS: Brain tissue obtained

    from male Sprague Dawley rats (n=7) was sectioned onto polysine slides

    and D2Rs were visualised by competition autoradiographic techniques

    using 20nM [3H]raclopride. D2R binding density was quantified in the

    ventral tegmental area (VTA) and nucleus accumbens (NAc) (mesolimbic

    pathway), substantia nigra (SN) and caudate putamen (CPU) (nigrostriatal

    pathway). The mean results of 7 animals were combined for each region

    of interest. RESULTS: Aripiprazole had a high affinity for the D2R in all

    regions examined. Aripiprazole had mean inhibition constants (Ki) of:

    15nM in the VTA, 71nM in the NAc, 21nM in the SN, 29nM in the CPU.

    CONCLUSION: Aripiprazole has a high binding affinity for the D2R in

    specific nuclei of the dopaminergic pathways in the rat brain. Aripiprazole

    affinity for D2Rs in the NAc was slightly lower than the other regions

    of interest; however values were similar in range, therefore differences

    in binding affinity cannot explain its reduced EPS. The mechanisms by

    which aripiprazole achieves its therapeutic effects, while avoiding EPS,

    require further investigation.

Publication Date


  • 2013

Citation


  • Weston-Green, K. & Deng, C. (2013). Binding affinity of aripiprazole to the dopamine D2 receptor in different regions of the rat brain. 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/903

Start Page


  • 115

End Page


  • 115

Place Of Publication


  • Australia