The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys.
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.
Ramos
Brian P
BP
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8001, USA.
Colgan
Lesley
L
Nou
Eric
E
Ovadia
Shira
S
Wilson
Steven R
SR
Arnsten
Amy F T
AF
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001288:Attention / Q000187:drug effects; D015784:Betaxolol / Q000494:pharmacology* / Q000633:toxicity; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives; D008253:Macaca mulatta; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D008845:Microinjections; D010182:Pancreatic Diseases / Q000139:chemically induced; D017397:Prefrontal Cortex; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D013238:Stereotaxic Techniques
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D006993:Hypnotics and Sedatives; D015784:Betaxolol