NORADRENALINE-SEROTONIN INTERACTIONS IN THE ANXIOLYTIC EFFECTS OF 5-HT1A AGONISTS

The purpose of this study was to analyse adrenergic and serotonergic interactions in the anxiolytic effects of several 5-HT1A agonists including ipsapirone, buspirone, indorenate and 8-OH-DPAT. To this end, the effects of different doses of the adrenergic compounds clonidine (0.015-0.0625 mg/kg), yohimbine (0.125-0.5 mg/kg), prazosin (0.5-2.0 mg/kg), pindolol (1.55-6.2 mg/kg) and practolol (0.25-1.0 mg/kg) on defensive burying behaviour were established. Clonidine (0.015-0.0625 mg/kg), prazosin (1.0 and 2.0 mg/kg), pindolol (1.55 and 6.2 mg/kg) and all 5-HT1A agonists reduced burying behaviour by themselves. In contrast, yohimbine (0.250 and 0.5 mg/kg) increased, while practolol did not modify, this behaviour. Additionally, the actions of yohimbine (0.125 mg/kg), prazosin (0.5 mg/kg), pindolol (3.1 mg/kg) and practolol (0.5 mg/kg) on the effects of ipsapirone (5.0 mg/kg), buspirone (5.0 mg/kg), indorenate (5.0 mg/kg) and 8-OH-DPAT (0.25 mg/kg) were examined. Prazosin enhanced the effects of ipsapirone, indorenate and buspirone, while yohimbine antagonized the actions of indorenate and 8-OH-DPAT. Pindolol enhanced the effects of indorenate while practolol antagonized the actions of ipsapirone, buspirone and 8-OH-DPAT. Only buspirone (5.0 mg/kg) affected motor coordination, an effect that was not counteracted by the antagonists. Based on these data an interaction between 5-HT1A agonists and the noradrenergic system in the regulation of anxiety is proposed.