Alpha 1- and beta-adrenoceptor stimulation potentiate the anticonflict effect of a benzodiazepine.
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 (0.5 mg/kg) which did not alter the behavior by itself, the alpha 2-adrenoceptor antagonist yohimbine consistently was found to enhance the anticonflict effect of APZ (0.5 mg/kg). The yohimbine induced potentiation of the APZ effect was counteracted both by the selective alpha 1-adrenoceptor antagonist prazosin (0.25 mg/kg) and the beta-adrenoceptor antagonist propranolol (2.0 mg/kg), but not by the selective beta 1-adrenoceptor antagonist metoprolol (2.0 mg/kg). Similar potentiating phenomena were obtained after co-administration of APZ (0.5 mg/kg) with the selective alpha 1-adrenoceptor agonist ST 587 (0.5-1.0 mg/kg) as well as with the suggested beta 2-adrenoceptor agonist clenbuterol (1.0 mg/kg). The results indicate that the potentiative effects of alpha 2-adrenoceptor antagonists on BDZ induced anticonflict action may be due to increased stimulation of alpha 1- and beta-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.
Söderpalm
B
B
Department of Pharmacology, University of Göteborg, Sweden.
Engel
J A
JA
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D011433:Propranolol; D011224:Prazosin; D000525:Alprazolam