Participation of D1–4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe6 angiotensin IV

Angiotensin IV (Ang IV) and des-Phe6Ang IV are naturally occurring neuroactive peptides of the renin-angiotensin system (RAS) involved in memory processing. However, the relevant mechanisms are poorly understood. In this review it is proposed that the pro-cognitive effects of these peptides are, at least partly, mediated by dopamine (DA). Recent studies demonstrated that the improvement of several memory aspects; recall of appetitively and aversively motivated behaviors and learning of spatial tasks by Ang IV and des-Phe6Ang IV was abolished, or significantly diminished by behaviorally inactive per se doses of the D1 and D2 receptor blockers SCH 23390 (R-[+]-7-chloro-8-hydroxy-3methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and remoxipride, respectively. The D3 receptor inhibition with nafadotride was almost ineffective but again, the D4 receptor blockade by L745,870 hydrochloride (3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine hydrochloride) diminished all, except for spatial memory, improving actions of the peptides. These results suggest that Ang IV and des-Phe6Ang IV enhance memory in a brain region-specific manner, dependent on local DA receptor subpopulations and the memory aspects controlled by them. The data reviewed here, demonstrating DA-Ang IV and des-Phe6Ang IV interactions in brain, strongly suggest probability of clinically relevant effects of concomitant use of antipsychotic and RAS affecting drugs.