?2-Adrenoceptor antagonists potentiate the anticonflict and the rotarod impairing effects of benzodiazepines

Abstract

Putative interactions between the specific alpha 2-adrenoceptor antagonist idazoxan and benzodiazepines (BDZs) were examined in two different rat conflict models; Vogel's drinking conflict test (VT) and Montgomery's conflict test (MT) (the elevated +-maze). In the MT, idazoxan (0.031 mg/kg) produced anxiogenic-like effects, which were counteracted both by the triazolo-BDZ alprazolam (APZ; 0.2 mg/kg) and the conventional BDZ diazepam (DIZ; 0.2 mg/kg). In fact, the anxiolytic-like effects of APZ were significantly potentiated when co-administering idazoxan. A tendency to such a phenomenon was seen also in rats treated with DIZ and idazoxan. In the VT, the anxiolytic-like effects both of APZ (1.0 mg/kg) and DIZ (4.0 mg/kg) were significantly enhanced when co-administering idazoxan (1.0 mg/kg) in a dose not affecting the behavior per se. Similar potentiating phenomena by behaviorally inert doses of alpha 2-adrenoceptor antagonists (idazoxan 1.0 mg/kg; yohimbine 2.0 mg/kg) were seen with regard to the ataxic/sedative effects of the BDZs (APZ 0.25 mg/kg; DIZ 1.5 mg/kg). The present results provide further support for the notion that the anxiolytic-like effects of BDZs are not related to attenuation of Locus Coeruleus activity. In addition, it is suggested that the potentiation caused by the alpha 2-adrenoceptor antagonist is mediated via a noradrenaline induced increase in signal-to-noise ratio in target neurons of the brain noradrenergic system.