A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex

Background: Stress exacerbates many neuropsychiatric disorders associated w ith prefrontal cortical (PFC) dysfunction. Stress also impairs the working memory functions of the PFC. Although stress research has focused an dopami nergic mechanisms, stress also increases norepinephrine (NE) release in PFC , and intra-PFC infusions of NE alpha-1-adrenoceptor agonists impair workin g memory. The current study examined whether NE alpha-1-adrenoceptor action s in PFC contribute to stress-induced deficits in working memory performanc e. Methods: Rats were treated with a pharmacological stressor, FG7142 (30 mg/k g) or vehicle 30 min before testing on a test of spatial working memory, de layed alternation. The alpha-1-adrenoceptor antagonist, urapidil (0.1 mu g/ 0.5 mu L), or saline vehicle, was infused into the PFC 15 min before delaye d alternation testing. Results: As observed previously, FG7142 significantly impaired the accuracy of delayed alternation performance, and induced a perseverative pattern of responding consistent with PFC dysfunction, FG7142 also slowed motor respo nse times. Infusion of urapidil into the PFC completely reversed the FG7142 -induced impairment in delayed alternation performance, but did not alter t he slowed motor responding. Conclusions: These findings indicate that alpha-1-adrenoceptor stimulation in the PFC contributes to stress-induced impairments in PFC cognitive funct ions. These neurochemical actions may contribute to symptoms of working mem ory impairment, poor attention regulation, or disinhibited behaviors in neu ropsychiatric disorders sensitive to stress exposure. (C) 1999 Society of B iological Psychiatry.