Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys

Most studies of cortisol-induced cognitive impairments have focused on hipp ocampal-dependent memory. This study investigates a different aspect of cog nition in a randomized placebo-controlled experiment with monkeys that were treated with cortisol according to a protocol that simulates a prolonged s tress response. Young adult and older adult monkeys were assigned randomly to placebo or chronic treatment with cortisol in a 2 x 2 factorial design ( n = 8 monkeys per condition). Inhibitory control of behavior was assessed w ith a test shown previously in primates to reflect prefrontal cortical dysf unction. Failure to inhibit a specific goal-directed response was evident m ore often in older adults. Treatment with cortisol increased this propensit y in both older and young adult monkeys. Age-related differences in respons e inhibition were consistent across blocks of repeated test trials, but the treatment effects were clearly expressed only after prolonged exposure to cortisol. Aspects of performance that did not require inhibition were not a ltered by age or treatment with cortisol, which concurs with effects on res ponse inhibition rather than nonspecific changes in behavior. These finding s lend support to related reports that cortisol-induced disruptions in pref rontal dopamine neurotransmission may contribute to deficits in response in hibition and play a role in cognitive impairments associated with endogenou s hypercortisolism in humans.