AT2 but not AT1 receptor antagonism abolishes angiotensin II increase of the acquisition of conditioned avoidance responses in rats (original) (raw)
Related papers
Angiotensin II Delays The Extinction of Active Avoidance in Rats The Role of Transmitter Receptors
The extinction of active avoidance behaviour in rats following the intracerebroventricular (ICV) injection of different doses of angiotensin II (Ang II) was studied. The influence of antagonists of different neurotransmitter receptors on the effects of Ang II was also followed. Ang II induced a delay in the extinction in a dose-dependent fashion (U-shaped curve). When the animals were pretreated with different receptor blockers in doses which themselves had no action on the extinction of active avoidance behaviour, the action of Ang II on this paradigm was completely blocked by saralasin, haloperidol, bicuculline, atropine, naloxone Phenoxybenzamine, propanolol and methysergide were ineffective. The data suggest that Ang II delays the extinction of active avoidance behaviour, and that angiotensin, dopamine, GABAa, opiate might be involved in this action.
Angiotensin II disrupts inhibitory avoidance memory retrieval
Hormones and Behavior, 2006
The brain renin-angiotensin system (RAS) is involved in learning and memory, but the actual role of angiotensin II (A II ) and its metabolites in this process has been difficult to comprehend. This has been so mainly due to procedural issues, especially the use of multi-trial learning paradigms and the utilization of pre-training intracerebroventricular infusion of RAS-acting compounds. Here, we specifically analyzed the action of A II in aversive memory retrieval using a hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Rats bilaterally implanted with infusion cannulae aimed to the CA1 region of the dorsal hippocampus were trained in IA and tested for memory retention 24 h later. We found that when given into CA1 15 min before IA memory retention test, A II , but not angiotensin IV or angiotensin 1-7 induced a dose-dependent and reversible amnesia without altering locomotor activity, exploratory behavior or anxiety state. The effect of A II was blocked in a dose-dependent manner by the A II -type 2 receptor (AT 2 ) antagonist PD123319 but not by the A IItype 1 receptor (AT 1 ) antagonist losartan. By themselves, neither PD123319 nor losartan had any effect on memory expression. Our data indicate that intra-CA1 A II hinders retrieval of avoidance memory through a process that involves activation of AT 2 receptors.
There is increasing interest in the potential functional role of the octapeptide angiotensin II (AII) in psychiatric and cognitive disorders. The novel angiotensin II (AII) receptor antagonists, losartan and PD 123177, selective for the AT1 and AT2 receptor sub-types respectively, constitute important pharmacological tools for the assessment of the behavioural consequences of modulation of AII function. The present series of studies investigated the effects of each compound in two animal models of anxiety, the rat elevated zero-maze and mouse light/dark box, and two models of working memory in the rat, the operant delayed matching to position (DMTP) task and the spatial reinforced alternation test in the T-maze. Our data indicate that both compounds (0.01 10mg/kg SC) were without significant effect in any of the behav-ioural assays. Using the present methods and strains of laboratory rodents, these findings provide no support for the involvement of AII receptor function in the mediation of anxiety or working memory.
Behavioural Brain Research, 2001
The functional interaction between ANG (3-8) (ANG IV) and adenosine A 1 receptor related drugs in passive avoidance (step-through) task in rats was studied in Wistar rats. ANG IV exerted dose-dependent (inverted-U) improvement of the retention while sarilesin (an angiotensin II analog) impaired this effect. Co-administration of theophylline and ANG IV, both in ineffective doses, enhanced the retention. The selective adenosine A 1 receptor agonist cyclopentyladenosine (CPA) attenuated ANG IV-induced memory enhancement.
Angiotensin II blocks memory consolidation through an AT 2 receptor-dependent mechanism
Psychopharmacology, 2005
Rationale and objectives Several studies suggest that the brain renin–angiotensin system is involved in memory consolidation. However, the participation of angiotensin II (AII) in this process is controversial. This is probably due to the fact that many of the studies carried out to elucidate this matter employed multitrial learning paradigms together with pretraining intracerebroventricular infusions, and therefore were unable to distinguish between consolidation and retrieval related events and lacked anatomical specificity. To circumvent this problem, we analyzed the role played in memory consolidation by AII using the hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Methods and results Rats bilaterally implanted with infusion cannulae into the CA1 region of the dorsal hippocampus (CA1) were trained in IA and tested for memory retention 24 h later. We found that when infused into CA1 immediately or 30 min after training but not later, AII produced a dose-dependent amnesic effect without altering locomotor activity, exploratory behavior or anxiety state. The amnesic effect of AII was not mimicked by angiotensin IV (AIV) and was totally blocked by the AII-type 2 receptor (AT2) antagonist, PD123319, but not by the AII-type 1 receptor (AT1) antagonist, losartan. Importantly, when infused alone, neither PD123319 nor losartan produced any effect on memory retention. Conclusions Our data indicate that, when given into CA1, AII blocks memory formation through a mechanism involving activation of AT2 receptors; however, endogenous AII does not seem to participate in the consolidation of IA long-term memory.
Neuroscience, 2004
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 peptidetreated 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.
2018
Objective(s): Stress alters sensory and cognitive function in humans and animals. Angiotensin (AT) receptors have demonstrated well-established interactions in sets of physiological phenomena. AT1 receptors can play a part in stress-induced activation of hypothalamic-pituitary-adrenal (HPA) axis; besides angiotensinergic neurotransmission plays a pivotal role in stress-evoked physiological responses. AT1 receptors are also involved in nociception and memory. The objective of the current study was to evaluate the effects of losartan as an AT1R antagonist in locomotor activity, nociception and memory impairments induced by sub-chronic swim stress. Materials and Methods: A two-session forced swimming stress protocol was administered to the rats. Pretreatment with losartan (10 mg/kg, IP) or saline was made before each swimming session. Locomotor activity, anxiety-like behavior, nociception, and passive avoidance learning were evaluated 24 hr after last swim stress session. Results: Swim...
Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1991
Characterization and development of angiotensin II receptor subtypes (AT1 and AT,) in rat brain. Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R209-R216, 1991.-Angiotensin II receptor subtypes (AT1 and AT,) were characterized in rat brain by displacement with the specific angiotensin antagonists Du Pont 753 and CGP 42112A, respectively, and quantitative autoradiography. Young (2-wk-old) rats expressed AT1 receptors in selected limbic system areas, structures involved in cardiovascular and fluid regulation, parts of the hippocampal formation, and the choroid plexus. In young rats, AT, receptors were concentrated in areas involved in control and learning of motor activity, sensory areas, and selected limbic system structures. The cingulate cortex, the molecular layer of the cerebellar cortex, and the superior colliculus contained both ATI and AT, receptors. The number of ATI receptors in most areas of adult (&wk-old) rats was similar to or even higher than that present in young rats. Conversely, AT, receptors were always much lower in number in adult animals, and in some areas they were undetectable in adults. Their differential localization and development suggest different functions for the specific angiotensin II receptor subtypes. angiotensin receptor subtypes; Du Pont 753; CGP 42112A; renin-angiotensin system; receptor development IN ADULT RATS, the brain angiotensin II (ANG II) system, including specific ANG II receptors located in very select areas, is involved in the central regulation of cardiovascular function, drinking and fluid metabolism, salt appetite, vasopressin release, and stress (4, 5, 13, 14, 21, 23, 24). Peripherally formed ANG II, present in the has been proposed on the basis of the response of smooth muscle to ANG II synthetic analogues (19). More recently, terized two subtypes in peripheral of ANG II receptors were charactissues on the basis of their sensitivity to reducing agents (7, 10-12) and their displacement with newly developed specific ANG II antagonists (6, 8, 9, 30). AT, receptors are sensitive to the reducing agent dithiothreitol (DTT) (7,9-12) and to displacement by the selective ANG II antagonist Du Pont 753 (8, 9). ANG II binding to the AT, receptors is resistant to DTT and selectively displaced by the ANG II-receptor antagonist CGP 42112A (30). Q uantitative autoradiography and displacement with the selective ANG II-receptor antagonists revealed that the rat brain contains AT1 receptors lot ular nucleus ated in the s , nucleus of ubfornical organ, pa the solitary tract, raven and tricarea postrema and AT, receptors localized in the inferior olive (27). The characteristics of the brain AT1 and AT2 receptors was similar to those described in peripheral organs (27). We have in the inferior recently shown by autoradiography that, olive, parasolitary and hypoglossal nuclei, and cerebellar cortex, the brain of young rats expresses more ANG II receptors than that of adult animals (28) and that, in the inferior olive of young and adult rats, the binding is insensitive to DTT (29). These observations suggested that young rats may express more AT, receptors than their adult controls. To determine the detailed developmental pattern of the receptor subtypes throughout the brain, we studied all areas containing significant numbers of ANG II receptors and compared their distribution and sensitivity to selected ANG II general circulation, binds to brain ANG II receptors antagonists in young (2-wk-o located in circumventricular organs outside the blood-rats. brain barrier (16, 21, 22) and contributes to the central regulation of cardiovascular function and fluid homeo-MATERIALS AND METHODS
Journal of Human Hypertension, 2002
Biochemical, physiological and functional studies suggest that the brain renin-angiotensin system (RAS) is regulated independently of the peripheral RAS. The classical actions of angiotensin II in the brain include blood pressure control, drinking behaviour, natriuresis and the release of vasopressin into the circulation. At least two subtypes of G-protein coupled receptors, the AT 1 and the AT 2 receptor, have been identified. Most of the classic actions of angiotensin II in the brain are mediated by AT 1 receptors. The AT 2 receptor is involved in brain development and neuronal regeneration and protection. Additionally, AT 2 receptors can modulate some of the classic angiotensin II actions in the brain. Selective non-peptide AT 1 receptor blockers, applied systemically, have been shown to inhibit both peripheral and brain AT 1 receptors. In genetically hypertensive rats, inhibition of brain AT 1 receptors may contribute to