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Does not support clinical use of central AT1/AT2 blockade for cognition; leaves open receptor roles in rodent memory models.
In this study I attempted to assess, in rats, the role of AT1 and AT2 angiotensin receptor subtypes in the phenomenon of improved learning and memory after an intracerebroventricular (icv) injection of angiotensin II (Ang II) and Ang II (3-7). Selective AT1 (losartan, 1 mg) or AT2 (CGP 42112 A, 2 micrograms) receptor antagonist was dissolved in 2 microliters of saline and given to the left cerebral ventricle 5 min before 1 nmol Ang II or Ang II (3-7) injected in the same volume of saline to the right ventricle. Consequently, there were 9 experimental groups which underwent 3 memory oriented and 3 auxiliary tests. Ang II and Ang II (3-7) significantly improved retention of the passive avoidance and recognition memory. These effects were abolished by losartan or CGP 42112 A. Better, after Ang II and Ang II (3-7), acquisition of conditioned avoidance responses was unchanged by losartan and abolished by CGP 42112 A. None of the treatments significantly changed rats motor behaviour in open field. Losartan as well as CGP 42112 A abolished significant enhancement of apomorphine (1 mg/kg, i.p.) stereotypy caused by Ang II and Ang II (3-7). The results suggest considerable involvement of AT1 and AT2 angiotensin receptors in the cognitive enhancement produced by angiotensins.
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Jan J. Braszko (1996) studied this question.
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