Abstract
Our previous studies showed that D(1) and D(2) dopamine receptors are indispensable for the cognitive effects of angiotensin IV (Ang IV) and its des-Phe(6) derivative des-Phe(6)-Ang IV to occur. As most neuroleptics currently used in the treatment of schizophrenia have variable D(2)/D(3) dopaminolytic selectivity, in this study we searched for the role of the D(3) dopamine receptors in facilitating learning and improving memory actions of Ang IV and des-Phe(6)-Ang IV in rats. For this purpose, we evaluated the recall of the passive avoidance (PA) behaviour, object recognition (OR) memory, and the spatial working memory (WM) in rats treated with the intraperitoneal (i.p.) nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide), a highly selective D(3) receptor blocker and then by an intracerebroventricular (i.c.v.) Ang IV or des-Phe(6)-Ang IV. Separate groups of rats receiving the same treatments were run to check for the possible participation of unspecific motor (open field) or emotioned (elevated "plus" maze) effects of our treatments in the results of the cognitive tests. The results revealed Ang IV to express its improving recall of PA, OR memory and WM action roughly similarly in all groups showing only minor or null significance of the D(3) receptors blockade. Interestingly, in the nafadotride pretreated rats, des-Phe(6)-Ang IV beneficial effect on the recall of the PA was weaker than that of Ang IV. Improvement of the spatial WM in an eight-arm radial maze, similar after Ang IV and des-Phe(6)-Ang IV, was not significantly affected by nafadotride. There were no motor and only minor anxiogenic effects of Ang IV and des-Phe(6)-Ang IV abolished by nafadotride in the former case. In conclusion, this study points to the minor significance of the D(3) dopamine receptors in the cognitive effects of Ang IV and to the interesting, though unexplained, inhibition by nafadotride of the des-Phe(6)-Ang IV effects.
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