Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat

Abstract

The effects of some 5-HT receptor ligands were investigated on measures of anxiety in an elevated plus-maze test in the rat. Quipazine (2 and 4 mg kg⁻¹), a non-specific 5-HT agonist and ritanserin (0ṁ25-10 mg kg⁻¹), a 5-HT₂ receptor antagonist displayed anxiogenic profiles by reducing both of the measures of anxiety used in this test. Two 5-HT_1A receptor ligands, buspirone (4 and 8 mg kg⁻¹) and ipsapirone (2.5-10 mg kg⁻¹) and the 5-HT₁ agonist, RU 24969 (0ṁ1875-1ṁ5 mg kg⁻¹) significantly reduced only the percentage of time spent on the open arms. (-)-Propranolol (5 and 10 mg kg⁻¹), a 5-HT₁ receptor antagonist significantly reduced only the percentage of entries made onto the open arms. Metergoline (4 mg kg⁻¹), a non-specific 5-HT antagonist displayed anxiolytic effects in this test by increasing both measures of anxiety. The 5-HT_1A receptor agonist, 8-OH-DPAT (0ṁ0625-0dependent manner in25 mg kg⁻¹) had no effect on either of the measures of anxiety. The results from the non-specific ligands (quipazine and metergoline) are consistent with the theory that a reduction in 5-HT function reduces anxiety. However, in spite of their more selective effects on 5-HT receptors the results in this test from the more specific ligands are not consistent with a strong involvement of any single receptor subtype. The interaction studies with yohimbine and FG 7142 (β-carboline-3-carboxylate methylamide) provided no clear evidence for a major role of 5-HT pathways in the mediation of their anxiogenic effects.