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

Kenya Medical Research Institute, PO Box 54840, Nairobi, Kenya

Martyn A. E. Critchley

Pharmacology Department, Wellcome Research Laboratories, Beckenham, Kent

Sheila L. Handley

Pharmacology Research, Pharmaceutical Sciences Institute, Aston University, Birmingham B4 7ET, UK

Effects of ß-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 ß₁-adrenoceptor antagonist metoprolol nor the ß ₂-adrenoceptor antagonist ICI 118,551 affected OTR or total entries. The peripherally acting ß₁-antagonist practolol was also inactive. The elevated X-maze therefore does not appear to detect ß-adrenoceptor-mediated changes in 'anxiety'. Among the ß-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.

Key Words: ß-adrenoceptors • agonist • antagonist • X-maze • 8-OH-DPAT

Journal of Psychopharmacology, Vol. 7, No. 2, 173-180 (1993)
DOI: 10.1177/026988119300700205


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