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PubMed · 9894572

Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function.

A F Arnsten·R Mathew·R Ubriani·J R Taylor·B M Li
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Abstract

BACKGROUND: Many neuropsychiatric disorders are associated with high levels of noradrenergic turnover, and most antipsychotic medications have alpha-1 adrenoceptor blocking properties, yet little is known about alpha-1 influences on higher cortical function. METHODS: The alpha-1 adrenergic agonist, phenylephrine, was infused into the prefrontal cortex (PFC) of rats (0.1 microgram/0.5 microL) performing a spatial working memory task, delayed alternation. The phenylephrine response was challenged with coinfusion of the alpha-1 adrenergic antagonist, uripidil (0.01 microgram), or with a dose of lithium chloride (4 mEq/kg, i.p., 18 hours) known to suppress phosphotidylinositol (PI) turnover, the second messenger pathway coupled to alpha-1 adrenoceptors. RESULTS: Phenylephrine infusions in PFC markedly impaired delayed alternation performance. The phenylephrine response was reversed by coinfusion of uripidil, or by pretreatment with lithium, consistent with actions at alpha-1 adrenoceptors coupled to a PI pathway. CONCLUSIONS: These findings demonstrate that alpha-1 adrenoceptor stimulation in the PFC impairs cognitive function. Excessive stimulation of alpha-1 adrenoceptors may contribute to PFC deficits (e.g., distractibility, impulsivity) in disorders such as mania, dementia, and anxiety associated with high noradrenergic turnover.

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Adrenergic alpha-1 Receptor AgonistsAdrenergic alpha-AgonistsAdrenergic alpha-AntagonistsAnimalsCognitionLithium ChlorideMaleNorepinephrinePhenylephrinePhosphatidylinositolsPiperazinesPrefrontal CortexPsychomotor PerformanceRatsRats, Sprague-DawleyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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A F Arnsten, R Mathew, R Ubriani, J R Taylor, B M Li. 1999-01-01. Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function.. https://doi.org/10.1016/s0006-3223(98)00296-0

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Adrenergic alpha-1 Receptor Agonists↗
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