Pergsmon Pharmacology Biochemistry and Behavior,Vol. 52, No. 1, pp. 231-236,1995 Copyright c 1995 Blsevier ScienceLtd Printed in the USA. All rights reserved 0091-3057/95 $9.50 + .ocl 0091-3057(95)00110-7 The Effects of Different Doses of Caffeine on Habituation of the Human Acoustic Startle Reflex EDWARD J. SCHICATANO* AND TERRY D. BLUMENTHAL?’ *Neuroscience Program, Bowman Gray School of Medicine, Winston-Salem, NC27157 TDepartment of Psychology, Wake Forest University, Winston-Salem, NC 27109 Received 10 June 1994 SCHICATANO, E. J. AND T. D. BLUMENTHAL. The zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGF effects of different doses of caffeine on habituation of the human acoustic startle reflex. PHARMACOL BIOCHEM BEHAV 52(l) 231-236, 1995.-Research in this laboratory showed that caffeine (4 mg/kg) delays habituation of the acoustic startle reflex in humans. The present study examined the effects of 2- and 6-mg/kg doses of caffeine on acoustic startle habituation in moderate-high and low caffeine users. Eyeblink responses to 30 trials of 85-dB noise stimuli were measured beginning 30 min after oral ingestion of either placebo or 2 or 6 mg/kg of caffeine. The 2-mg/kg dose of caffeine delayed startle habituation in both moderate-high and low caffeine users. The 6-mg/kg dose produced no differential effects on startle responding from placebo. In moderate-high users, following habituation, startle responding was smaller in the placebo condition compared to both caffeine conditions. In low users there were no differences in posthabituation responding between doses, suggesting that this dose effect is dependent on a history of chronic caffeine usage. Caffeine Startle Habituation Humans Arousal Brainstem Reflex CAFFEINE is a widely used psychoactive substance (21) and has been studied using a variety of cognitive/behavioral tasks (12,14,15). In humans, caffeine has been shown to improve vigilance and performance on cognitive tasks (12,14), enhance sustained visual attention (23), and reverse the negative effects of sleep deprivation on mood and alertness (16). It has been hypothesized that caffeine interacts with a multitude of vari- ables, such as user level, type of environment (novel vs. bor- ing), and dose, in producing some of these cognitive/behav- ioral effects (19). Using psychophysiologic measures in humans, several re- searchers have reported that caffeine increases skin conduc- tance in a dose-related manner (5,6,19). Davidson et al. (6) and Smith et al. (19) reported that caffeine enhances physio- logic responses to redundant external stimuli (i.e., caffeine reduces habituation of the skin conductance response). Specif- ically, in both moderate-high and low caffeine users, caffeine slowed habituation of skin conductance to auditory stimuli (19). These results are similar to those of Wolpaw and Penry (24), who found that caffeine prevented a decrease in NlP2 amplitudes to auditory-evoked responses caused by habitua- tion. Using the acoustic startle paradigm in humans, Schica- tano and Blumenthal (17) showed that caffeine delays habitua- tion of the acoustic startle reflex without affecting the size of the initial response. Together, these findings indicate that caffeine produces persistent responding to redundant stimula- tion (i.e., caffeine delays habituation). The reported effects of caffeine on psychophysiologic mea- sures such as the skin conductance response and evoked poten- tials suggest that caffeine may increase arousal (6,19,24). It is therefore possible that the effects of a 4-mg/kg dose of caf- feine on startle habituation may be due to increases in arousal (17). If caffeine modulates startle habituation by increasing arousal, then varying the caffeine dose should produce differ- ential effects on startle. Specifically, caffeine dose effects should resemble an inverted U-shaped relationship that is commonly reported in the arousal literature. To test this the- ory, the present experiment assessed the effects of placebo and 2- and 6-mg/kg doses of caffeine on startle. In the case of startle habituation, a high dose of caffeine would produce ’ Requests for reprints should be addressed to Terry D. Blumenthal, Department of Psychology, Wake Forest University, Box 7778 Reynolda Station, Winston-Salem, NC 27109. 231