D2 dopamine receptor blockade prevents cognitive effects of Ang IV and des-Phe6 Ang IV

Angiotensins, especially angiotensin IV (Ang IV), have recently been found to be potent cognitive enhancers in rodents. However, the precise mechanisms of their memory improving effects remain unknown. In this study we tested the hypothesis that D2 dopamine receptors at least partially mediate cognitive effects of Ang IV and its derivative des-Phe6 Ang IV. Namely, the well known cognitive effects of both peptides [facilitation of a conditioned avoidance responses (CARs) acquisition, increase of a passive avoidance behavior (PAB) retrieval, and improvement of object recognition] were evaluated in rats either pretreated or not with a selective D2 dopamine receptor antagonist remoxipride {(S)-(−)-3-Bromo-N-[(1-ethyl-2-pyrrolidinylOmethyl]2,6-dimethoxybenzamide hydrochloride}. To control for the unspecific motor and emotional effects of our treatments that could confound results of the memory tests we used respectively, 'open' field and elevated 'plus' maze tests. Ang IV as well as des-Phe6 Ang IV remarkably improved learning of CARs, recall of PAB and recognition of the previously seen objects. D2 receptors blockade by remoxipride abolished all these effects of both peptides. In the elevated 'plus' maze remoxipride abolished anxiogenic effects of both Ang IV and des-Phe6 Ang IV. Also, the drug followed by Ang IV decreased number of crossings and by des-Phe6 Ang IV number of crossings and rearings. The results point to importance of the functional D2 dopamine receptors in cognitive effects of Ang IV and its naturally occurring product devoid of C-terminal Phe6.