The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys

Biol Psychiatry. 2005 Dec 1;58(11):894-900. doi: 10.1016/j.biopsych.2005.05.022. Epub 2005 Jul 25.


Background: Previous studies have indicated that beta adrenergic receptor stimulation has no effect on the cognitive functioning of the prefrontal cortex (PFC). Blockade of beta-1 and beta-2 receptors in the PFC with the mixed beta-1/beta-2 antagonist, propanolol, had no effect on spatial working memory performance. However, more selective blockade of beta-1 or beta-2 receptors might show efficacy if the two receptors have opposite effects on PFC function. The current study examined the effects of the selective beta-1 antagonist, betaxolol, on working memory in rats and monkeys.

Methods: In rats, betaxolol (.0011-1.11 microg/.5 microL) was infused into the PFC 5 min before delayed alternation testing. Monkeys were systemically injected with betaxolol (.0000011-.11 mg/kg) 2 hours before delayed response testing.

Results: Betaxolol produced a dose-related improvement in working memory performance following either direct PFC infusion in rats, or systemic administration in monkeys. However, some aged monkeys developed serious pancreatic problems over the course of this study.

Conclusions: These findings suggest that endogenous activation of the beta-1 adrenergic receptor impairs PFC cognitive function. These results may have therapeutic relevance to post-traumatic stress disorder or other disorders with excessive noradrenergic activity and PFC dysfunction. Pancreatic side effects in aged subjects taking betaxolol warrants further investigation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists*
  • Adrenergic beta-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / toxicity
  • Animals
  • Attention / drug effects
  • Betaxolol / pharmacology*
  • Betaxolol / toxicity
  • Cognition / drug effects
  • Dose-Response Relationship, Drug
  • Hypnotics and Sedatives
  • Macaca mulatta
  • Male
  • Maze Learning / drug effects
  • Memory, Short-Term / drug effects*
  • Microinjections
  • Pancreatic Diseases / chemically induced
  • Prefrontal Cortex
  • Psychomotor Performance / drug effects*
  • Rats
  • Stereotaxic Techniques


  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Hypnotics and Sedatives
  • Betaxolol