ABSTRACT
We have previously shown that angiotensin II (Ang II) improves cognitive performance of rats. In this study, behavioral effects of trandolapril, a highly lipophilic antihypertensive drug efficiently inhibiting brain angiotensin converting enzyme (ACE), were examined in rats. Single (0.1, 0.5, 1.0 mg/kg) or repetitive (0.1 mg/kg daily for 14 days) doses of trandolapril were given orally. The medium dose of the drug administered acutely as well as the chronic treatment significantly attenuated acquisition of conditioned avoidance responses. None of the three doses of trandolapril changed consolidation of memory and recall of the passive avoidance behavior, object recognition, and locomotor exploratory activity in open field. These data point to the psychoactive properties of trandolapril and suggest that physiological levels of the endogenous Ang II may be required for effective learning.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , Avoidance Learning/drug effects , Indoles/pharmacology , Administration, Oral , Analysis of Variance , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Animals , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Indoles/administration & dosage , Male , Memory/drug effects , Rats , Rats, WistarABSTRACT
An involvement of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)] in rats was studied. To inhibit AT2 receptors we used their selective antagonist CGP 42112A (nicotinic acid-Tyr-N-benzoxyl-carbonyl-Arg-Lys-His-Pro-Ile-OH). Ang II and Ang II(3-7), given intracerebroventricularly (i.c.v.) at the dose of 1 nmol each, significantly enhanced recall of the passive avoidance behaviour and learning of the conditioned avoidance responses (CARs). CGP 42112A (2 micrograms i.c.v.), inactive on its own in all tests, significantly attenuated facilitation of recall of passive avoidance caused by Ang II and Ang II(3-7). Also, CGP 42112A diminished Ang II improvement of CARs acquisition but not that caused by Ang II(3-7). None of the treatments produced significant anxiolysis in an elevated 'plus' maze. Likewise, in an open field no statistically significant differences were recorded except for the abolishment of the Ang II(3-7)-induced increase of rearings and bar approaches by CGP 42112A. It appears that the cognition improving activity of Ang II and Ang II(3-7) is mediated by similar mechanisms and angiotensin AT2 receptors are engaged in these processes.
Subject(s)
Angiotensin II/antagonists & inhibitors , Avoidance Learning/drug effects , Mental Recall/drug effects , Oligopeptides/pharmacology , Peptide Fragments/physiology , Receptors, Angiotensin/physiology , Angiotensin Receptor Antagonists , Animals , Behavior, Animal/drug effects , Injections, Intraventricular , Male , Rats , Rats, WistarABSTRACT
The role of the angiotensin AT2 receptors in some behavioural effects of angiotensin II (Ang II) and its 3-7 fragment [Ang II(3-7)], using their selective antagonist CGP 42112A, was assessed. Ang II and Ang II(3-7), given intracerebroventricularly (icv) at the dose of 1 nmole each, substantially improved object recognition memory and enhanced apomorphine (1 mg/kg) stereotypy. Pre-treatment of rats with CGP 42112A (2 micrograms), per se ineffective in all tests, abolished activity of both peptides. None of the treatments significantly changed behaviour of rats in open field. The results point to the considerable involvement of the AT2 angiotensin receptors in the improvement of recognition memory caused by Ang II and Ang II(3-7).
Subject(s)
Angiotensin II/physiology , Oligopeptides/pharmacology , Pattern Recognition, Visual/drug effects , Pattern Recognition, Visual/physiology , Peptide Fragments/physiology , Animals , Behavior, Animal/drug effects , Locomotion/drug effects , Male , Memory/drug effects , Memory/physiology , Rats , Rats, WistarABSTRACT
We have previously shown that angiotensin II(3-7) [Ang II(3-7)] stimulates behavioural activity of rats similar to angiotensin II (Ang II). The involvement of AT1 angiotensin receptors in stimulating the behavioural activity of rats, using their selective ligand losartan (DUP 753), was examined. Ang II(3-7), given intracerebroventricularly (i.c.v.) at a dose of 1 nmol, significantly enhanced recall of a passive avoidance behaviour, object recognition, learning of conditioned avoidance responses (CARs) and apomorphine (1 mg kg-1, i.p.) stereotypy. Losartan (1 microgram, i.c.v.) did not alter any of the behaviours except for that measuring anxiety which was diminished both, in peptide treated and in control rats. On the other hand, losartan abolished Ang II(3-7) facilitation of recall of the passive avoidance, object recognition and the increase in apomorphine stereotypy. Losartan did not influence the increased rate of CARs acquisition after the peptide. None of the treatments significantly changed locomotor activity estimated in an open field. These data point to some involvement of AT1 angiotensin receptors in the behavioural activity of Ang II(3-7).
Subject(s)
Angiotensin II/pharmacology , Angiotensin Receptor Antagonists , Behavior, Animal/drug effects , Learning/drug effects , Losartan/pharmacology , Peptide Fragments/pharmacology , Animals , Male , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2ABSTRACT
All and rho-aminophenylalanine6 angiotensin II, given i.c.v. (1 nmol) enhanced memory and stereotypic behaviour leaving gross motor activity unchanged. Both peptides showed also some anxiogenic action.
