Involvement of D1 dopamine receptors in the cognitive effects of angiotensin IV and des-Phe6 angiotensin IV

An important role for angiotensin IV (Ana IV) in the processes of learning and memory has now been well established. We have previously found that intracerebroventricular (ICV) administration of Ana IV as well as des-Phe(6)-Ang IV enhances learning of conditioned avoidance responses (CARS), facilitates recall of a passive avoidance (PA) task, and improves object recognition (OR) in rats. Since the dopaminergic system is crucial for the cognitive processes, in this study our aim was to determine the dopaminergic D-1 mediation of these effects using SCH 23390 as a selective D, receptor antagonist. Male Wistar rats (180-200g), pretreated with SCH 23390 (R-[+]-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) 0.05 mg/kg intraperitoneally (IP), were given Ang IV or des-Phe(6)-Ang IV (1 nmol ICV) 1 h later and then tested in the above cognitive paradigms, as well as in the open field and an elevated 'plus' maze to control for the unspecific, respectively, motor and emotional, effects of our treatments. Both, Ana IV and des-Phe(6)-Ang IV effectively enhanced learning of CARs (P < 0.05), recall of PA (P < 0.001), and improved OR (P < 0.001). Pretreatment with SCH 23390 abolished the cognitive effects of both peptides. SCH 23390, Ana IV, and des-Phe(6)-Ang IV, given at the same doses and routes as in the cognitive tests, did not significantly influence crossings, rearings and bar approaches in the open field, nor the parameters measured in the elevated 'plus' maze, thus making a major contribution of the unspecific effects of our treatments to the results of the memory tests improbable. In conclusion, these results indicate that the functional dopaminergic D, receptors are necessary for the Ana IV and des-Phe(6)-Ana IV cognitive effects to occur. (C) 2004 Elsevier Inc. All rights reserved.