?1- and ?-adrenoceptor stimulation potentiate the anticonflict effect of a benzodiazepine

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Abstract
Interactions between different noradrenaline (NA)-active drugs and the benzodiazepine alprazolam (APZ) were examined in a modified Vogel's drinking conflict test in the rat. In a dose (0.5mg/kg) which did not alter the behavior by itself, the α2-adrenoceptor antagonist yohimbine consistently was found to enhance the anticonflict effect of APZ (0.5mg/kg). The yohimbine induced potentiation of the APZ effect was counteracted both by the selective α1-adrenoceptor antagonist prazosin (0.25mg/kg) and the β-adrenoceptor antagonist propranolol (2.0mg/kg), but not by the selective β1-adrenoceptor antagonist metoprolol (2.0 mg/kg). Similar potentiating phenomena were obtained after co-administration of APZ (0.5 mg/kg) with the selective α1-adrenoceptor agonist ST 587 (0.5–1.0 mg/kg) as well as with the suggested β2-adrenoceptor agonist clenbuterol (1.0 mg/kg). The results indicate that the potentiative effects of α2-adrenoceptor antagonists on BDZ induced anticonflict action may be due to increased stimulation of α1 and β-adrenoceptors,via enhanced NA release. The findings are discussed in relation to the signal-to-noise hypothesis of NA function, and in relation to the suggested NA involvement in anxiety-related behavior.