The effect of alpha-2 adrenergic agonists on memory and cognitive flexibility.
BACKGROUND
The noradrenergic system modulates cognitive flexibility for insight-based problem solving in studies using beta-adrenergic antagonists, which block noradrenergic neurotransmission postsynaptically. However, it is not known whether alpha2-adrenergic agonists, that decrease noradrenergic neurotransmission by presynaptic inhibition, have the same effect.


OBJECTIVE
Therefore, we wished to test whether alpha2-adrenergic agonists would have a similar effect on cognitive flexibility.


METHODS
Eighteen normal adults were tested on cognitive flexibility, problem solving, verbal and spatial memory tasks after receiving clonidine (0.1 mg), an alpha2-agonist, placebo, or ephedrine (25 mg), a noradrenergic stimulant.


RESULTS
Three-way analysis of variance revealed no significant drug effect on cognitive flexibility or problem solving. There was also no significant effect of clonidine on memory.


CONCLUSIONS
Therefore, alpha2-agonists do not influence cognitive flexibility in the same manner as beta-antagonists. Better performance on memory with clonidine might be expected based on primate studies demonstrating benefits in working memory using clonidine. This benefit was not observed for the commonly used clinical memory tasks in our study. This may have implications for why clonidine has not demonstrated efficacy for cognitive disorders such as Alzheimer disease, despite its known benefit for working memory in animal models.
Choi
Youngjee
Y
Washington University, St Louis, MO, USA.
Novak
John C
JC
Hillier
Ashleigh
A
Votolato
Nicholas A
NA
Beversdorf
David Q
DQ
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology*; D004809:Ephedrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D011340:Problem Solving / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D014706:Verbal Learning / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D004809:Ephedrine; D003000:Clonidine