Differential effects of aripiprazole and haloperidol on dopamine markers in the arcuate nucleus and prolactin levels in male rats
Objective : Aripiprazole is a new antipsychotic drug with a high affinity for dopamine D2 receptors but reduced risks for inducing extrapyramidal (EPS) and hyperprolactinaemia (HPL) side-effects. Our previous study (Han et al., 2009, International Journal of Neuropsychopharmacology 12 : 941–952) showed that aripiprazole selectively reduced the expression of tyrosine hydroxylase (TH; a rate-limiting enzyme for the synthesis of dopamine) in the ventral tegmental area (VTA) but not the substantia nigra (SN), suggesting a selective reduction of dopamine synthesis in the VTA but not SN. However haloperidol affected on both nuclei. Since the tuberoinfundibular dopamine neurons in the arcuate nucleus (Arc) modulate prolactin secretion, this study investigated the effects of aripiprazole on the expression of dopamine markers in the Arc and plasma prolactin levels following short and long-term treatment. As a comparison, the effects of haloperidol on these measurements were also examined. Methods : Male Sprague Dawley ratswere treated with aripiprazole (0.75mg/kg, t.i.d.), haloperidol (0.1mg/kg, t.i.d) or control (vehicle) for 1-week or 10-weeks (n=6/group). Protein levels of TH, phospho- TH (pTH) and dopamine transporter (DAT) in the Arc, as well as plasma prolactin levels, were examined. Results : Compared to controls, haloperidol significantly increased TH levels (p<0.01) after both short- and long-term treatment, and pTH and DAT after long-term treatment (p<0.05) ; however, aripiprazole had no significant effect on these dopamine markers in the Arc. Consistently, haloperidol (p<0.01), not aripiprazole, significantly increased plasma prolactin levels. Conclusion: Aripiprazole and haloperidol have different effects on the expressions of dopamine markers in the Arc and prolactin levels. These results support the selective effects of aripiprazole on dopamine synthesis in different dopamine pathways as a possible mechanism for the long-term efficacy of aripiprazole with low EPS and HPL sideeffects liability.
This record is in the process of being updated. Please contact us for more information.