Effects of prazosin on the dopaminergic neurotransmission in rat brain

Effects of systemic and local administration of prazosin, an alpha 1-adrenoceptor antagonist, on dopaminergic neurotransmission in the caudate putamen and nucleus accumbens were characterized in microdialysis experiments. Prazosin (10 mg/kg s.c.) resulted in blood pressure reduction, however, did not alter dopamine release in the two examined brain areas. In contrast, local administration of prazosin (10 microM) via the microdialysis probe resulted in a clear attenuation of dopamine output, indicating that tonically activated alpha 1-adrenoceptors stimulate dopamine release in the caudate putamen as well as in the nucleus accumbens. The relevance of this finding for antipsychotics exhibiting antagonism at alpha 1-adrenoceptors is discussed.