ANGIOTENSIN-II(3-8) (ANG-IV) HIPPOCAMPAL BINDING - POTENTIAL ROLE IN THE FACILITATION OF MEMORY

The present research characterizes a newly discovered ANG II(3-8) (ANG IV) binding site localized in structures associated with memory funct ion (hippocampus, neocortex, cerebellum), as well as other brain stem structures (thalamus, inferior olivary nucleus). This site is not the AT1 or AT2 site that binds angiotensins II (ANG II) and III (ANG III) nor does it bind the nonpeptide AT1 or AT2 receptor antagonists DuP753 and PD123177, respectively. The intracerebroventricular (ICV) infusio n of ANG IV was ineffective at inducing drinking in rats as compared w ith equivalent doses of ANG II and III. Although not as effective as A NG II or ANG III, ICV infusion of ANG IV did provoke a pressor respons e at the highest dose (100 pmol/min), which appeared to be mediated by ANG II (AT1)-type receptors and not the specific AIV binding site des cribed here. By contrast, the ICV infusion of ANG IV resulted in great er effects upon retention and retrieval of a passive avoidance task as compared with ANG II. Specifically, ANG II was not different from the ICV infusion of artificial cerebrospinal fluid, while ANG IV improved retention and retrieval of this task.