AT(2) but not AT(1) receptor antagonism abolishes angiotensin II increase of the acquisition of conditioned avoidance responses in rats.
In this study we attempted to determine behavioural, including cognitive, consequences of the brain AT(1) (losartan, 2 nmol), AT(2) (PD 123319, 1.5 nmol), and joint AT(1)/AT(2) angiotensin receptors blockade. Male Wistar rats (160-180 g) were injected into the left cerebral ventricle with the above doses of the blockers dissolved in 0.9% NaCl solution (vehicle) or with the vehicle alone. Five minutes later they received, to the right cerebral ventricle, 1 nmol of angiotensin II (Ang II) dissolved in vehicle or the vehicle alone. Ang II consistently increased rate of acquisition of conditioned avoidance response (CARs) and facilitated recall of the passive avoidance behaviour. In one out of the three series of experiments in open field Ang II stimulated rats locomotor activity. Losartan and PD 123319, both ineffective alone, given prior to Ang II abolished all the behavioural changes produced by the peptide except for the Ang II facilitation of CARs acquisition, which was unchanged by losartan. Interestingly, joint injection of losartan and PD 123319 significantly decreased the rate of CARs acquisition both in control and Ang II treated animals. In conclusion, the present data suggest significant though different involvement of both AT(1) and AT(2) angiotensin receptors in cognitive processes.
Braszko
Jan J
JJ
Department of Clinical Pharmacology, Medical Academy of Bialystok, Ludwik Zamenhof Childrens Hospital, J. Waszyngtona St. 15 A, 15-274, Bialystok, Poland. braszko@amb.ac.bialystok.pl
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan