Effects of beta-adrenoceptor ligands in the elevated X-maze 'anxiety' model and antagonism of the 'anxiogenic' response to 8-OH-DPAT

Abstract

Effects of β-adrenoceptor agonists and antagonists have been examined on open/total arm entry ratio (OTR) over a wide range of doses in the rat elevated X-maze 'anxiety' model. For clenbuterol, terbutaline and adrenaline, OTR was reduced only at doses at or above those reducing total entries; dobutamine was inactive. Neither the β₁-adrenoceptor antagonist metoprolol nor the β ₂-adrenoceptor antagonist ICI 118,551 affected OTR or total entries. The peripherally acting β₁-antagonist practolol was also inactive. The elevated X-maze therefore does not appear to detect β-adrenoceptor-mediated changes in 'anxiety'. Among the β-adrenoceptor antagonists which also bind to 5-HT₁ receptors, sotalol and timolol were inactive but restricted doses of alprenolol (0.1 mg/kg) and pindolol (0.1-0.25 mg/kg) caused an anxiolytic-like increase in OTR while propranolol (5-10 mg/kg) and pindolol (1.0 mg/kg) reduced OTR without affecting total entries. These effects may be attributable to the activity of these agents at 5-HT ₁ receptors. Since metoprolol (3.0 mg/kg) and ICI 118,551 (1.0 mg/kg) did not alter the fall in OTR caused by the selective 5-HT_1A agonist 8-OH-DPAT, the antagonism of this fall by alprenolol (0.5 mg/kg), pindolol (0.5 mg/kg), propranolol (3.0 mg/kg) and timolol (3.0 mg/kg) is most likely to represent a 5-HT₁ receptor antagonist effect of these agents.