Effects of chronic antipsychotic treatment on dopamine synthesis
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
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