122. Effects of caffeine on sensorimotor gating of the startle reflex in normal control subjects

Abstract

Prepulse inhibition (PPI), a cross-species measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. This study was designed to assess caffeine effects on PPI in normal humans, as part of an effort to understand cross-species differences and similarities in the neurochemical regulation of PPI. Startle was measured during a screening session (“DAY 1”); 7–10d later, subjects were retested (“DAY 2”) after placebo or caffeine (200 mg; double-blind design). Subjects, characterized as low vs. high caffeine drinkers (LOCAF vs. HICAF) based on established scales, refrained from ad libitum caffeine consumption for ≥ 15h prior to DAY 2 testing. Autonomic and self-rating measures, acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in divided sessions for 3h post-treatment. On DAY 2, there were significant effects of caffeine on autonomic measures but not acoustic or tactile startle magnitude, habituation or PPI. HICAF subjects reported withdrawal symptoms after placebo that were blunted by caffeine. Compared to DAY 1 measures, DAY 2 PPI was greater in LOCAF subjects after placebo, and in HICAF subjects after caffeine. The opposite pattern was also true: LOCAF subjects exhibited less PPI after caffeine, and HICAF subjects exhibited less PPI after placebo, on DAY 2 vs. DAY 1. Thus, caffeine withdrawal, evident in HICAF subjects after placebo, may be accompanied by reduced PPI. A new study is in progress in which subjects maintain ad libitum caffeine intake to blunt any impact of caffeine withdrawal on startle.