Effects of angiotensin II on dopamine and serotonin turnover in the striatum of conscious rats

Abstract

This study was designed to evaluate the functional significance of angiotensin II (Ang II) receptors identified by previous receptor autoradiography studies to be located presynaptically on terminals of dopaminergic neurones projecting to the striatum. Microdialysis was performed in the striatum of conscious freely moving rats and dopamine and serotonin metabolites measured by HPLC with electrochemical detection. During perfusion with artificial CSF, the major extracellular dopamine metabolite identified was DOPAC with smaller concentrations of HVA. When Ang II (1 microM) was introduced into the dialysis perfusion medium, DOPAC output increased markedly, peaking at 219%, and returned to control with vehicle perfusion during the recovery period. This increase in DOPAC output with Ang II was completely blocked by co-administration of the AT1 selective antagonist, Losartan (1 microM). Administration of Losartan alone led to a significant (16%) depression of DOPAC output relative to vehicle, suggesting that dopamine release is under a tonic facilitatory influence of Ang II via the AT1 receptor subtype. Parallel, but smaller changes were seen with HVA outputs. During Ang II perfusion the output of HVA was elevated 34-79% of that in vehicle-treated rats and this effect was completely abolished by concomitant administration of Losartan. As was observed with DOPAC output, administration of Losartan alone led to a 13-24% depression of HVA output compared to vehicle perfusion. When nomifensine (10 microM) was included in the infusion fluid, dopamine was clearly measurable. Ang II perfusion increased the levels of dopamine to 225%. Values returned towards baseline during the recovery period. Ang II administration also increased (by 15% and 55%) the levels of the major serotonin metabolite, 5HIAA.(ABSTRACT TRUNCATED AT 250 WORDS)