Effect of ICV injection of AT(4) receptor ligands, NLE1-angiotensin IV and LVV-hemorphin 7, on spatial learning in rats

Central administration of angiotensin IV (Ang IV) or its analogues enhance performance of rats in passive avoidance and spatial memory paradigms. The purpose of this study was to examine the effect of a single bolus injection of two distinct AT(4) ligands, Nle(1)-Ang IV or LVV-haemorphin-7, on spatial learning in the Barnes circular maze. Mean number of days for rats treated with either Nle(1)-Ang IV or LVV-haemorphin-7 to achieve learner criterion is significantly reduced compared with controls (P<0.001 and P<0.05 respectively). This is due to enhanced ability of the peptide-treated rats to adopt a spatial strategy for finding the escape hatch. In all three measures of learning performance, (1) the number of errors made, (2) the distance travelled and (3) the latency in finding the escape hatch, rats treated with either 100 pmol or 1 nmol of Nle(1)-Ang IV or 100 pmol LVV-haemorphin-7 performed significantly better than the control groups. As early as the first day of testing, the rats treated with the lower dose of Nle(1)-Ang IV or LVV-haemorphin-7 made fewer errors (P<0.01 and P<0.05 respectively) and travelled shorter distances (P<0.05 for both groups) than the control animals. The enhanced spatial learning induced by Nle(1)-Ang IV (100 pmol) was attenuated by the co-administration of the AT(4) receptor antagonist, divalinal-Ang IV (10 nmol). Thus, administration of AT(4) ligands results in an immediate potentiation of learning, which may be associated with facilitation of synaptic transmission and/or enhancement of acetylcholine release. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.