Strain differences in the anxiolytic effects of losartan in the mouse.
Anxiolytic effects of the angiotensin AT(1) receptor antagonist losartan were studied in the elevated plus maze (EPM) and the light/dark test (LDT) in different mouse strains as were responses to angiotensin II and acetylcholine in isolated ascending colon. There were no significant strain differences in behaviour on the EPM, and diazepam was anxiolytic in C57BL/6, DBA/2 and BKW mice. Losartan was anxiolytic in BKW only. In the LDT, there were significant strain differences, with BKW mice exhibiting greatest anxiety-like behaviour; losartan was ineffective in this test. In vitro responses to angiotensin II and acetylcholine were significantly smaller in BKW than in C57BL/6 and DBA/2. These results indicate that the mouse strain exhibiting least angiotensin receptor function is the most responsive to the anxiolytic effects, suggesting a possible relationship between angiotensin receptor function and anxiolytic response to losartan.
Gard
P R
PR
School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, BN2 4GJ, Brighton, UK. p.r.gard@brighton.ac.uk
Haigh
S J
SJ
Cambursano
P T
PT
Warrington
C A
CA
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D003106:Colon / Q000187:drug effects; D003624:Darkness; D066298:In Vitro Techniques; D008027:Light; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013045:Species Specificity
D057911:Angiotensin Receptor Antagonists; D014151:Anti-Anxiety Agents; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019808:Losartan