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

J Neural Transm Gen Sect. 1990;79(3):155-67. doi: 10.1007/BF01245127.

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 (0.5 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprazolam / pharmacology*
  • Animals
  • Conflict, Psychological*
  • Dose-Response Relationship, Drug
  • Male
  • Prazosin / pharmacology
  • Propranolol / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology*
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology*
  • Yohimbine / pharmacology*

Substances

  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Yohimbine
  • Propranolol
  • Prazosin
  • Alprazolam