Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Division of Psychiatry, Psychopharmacology Section, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Neuropsychopharmacology (Impact Factor: 7.05). 12/2007; 32(11):2405-21. DOI: 10.1038/sj.npp.1301363
Source: PubMed


A sudden loud sound evokes an electromyographic (EMG) response from the orbicularis oculi muscle in humans together with an auditory evoked potential (AEP) and an increase in skin conductance (SC). Startle responses are inhibited by weak prepulses (prepulse inhibition, (PPI)) and may also be modified by the level of alertness. We compared the sedative drug clonidine and the alerting drug modafinil on sound-evoked EMG, AEP, and SC responses, on the PPI of these responses and on level of arousal and autonomic functions. Sixteen healthy male volunteers participated in four weekly sessions (clonidine 0.2 mg, modafinil 400 mg, their combination, placebo) in a double-blind, cross-over, balanced design. Responses were evoked by sound pulses of 115 and 85 dB (PPI) for 40 ms and recorded conventionally. Level of alertness, autonomic functions (pupil diameter, blood pressure, heart rate, salivation, temperature) and the plasma levels of the hormones prolactin, thyroid-stimulating hormone and growth hormone were also measured. Data were analyzed with analysis of variance with multiple comparisons. Both prepulses and clonidine attenuated all three startle responses and modafinil antagonized clonidine's effects on the EMG and AEP responses. None of the drugs affected PPI. Clonidine showed sedative and sympatholytic effects, and modafinil showed alerting and sympathomimetic effects. In conclusion, startle responses were susceptible not only to PPI but also to the level of arousal.

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Available from: Ruihua Hou, Jun 06, 2014
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    • "The traction was considered as defense and startle response in humans or a fight/flight reaction in animals. The rise of cardiovascular parameters to acoustic startle stimulation suggested an autonomic function responding to the acoustic stimulation [34]. Moreover, cortical centers and also subcortical processing areas were supposed to be involved in the cardiovascular and hormonal responses to long-term stress activation by the environmental noises even though the noise intensity was as low as 53 dB [35]. "
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    • "Interestingly, the autonomic component of the startle reflex, like the motor component (see above), is subject to prepulse modulation (Samuels et al., 2007; Eder et al., 2009). Although the exact connections of this " sensorysympathetic reflex " are not known, it is likely that a number of premotor sympathetic nuclei, including the ventrolateral medulla (Holand et al., 1999), the LC and the hypothalamic paraventricluar nucleus (Samuels et al., 2007) are involved. "
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    • "The responses were regarded as a startle and defense response in humans or a fight/flight reaction in animals. The rise in the blood pressure and heart rate in response to acoustic startle stimuli indicates an autonomic function responding to the acoustic stimuli (22). Furthermore, cortical centers and subcortical processing centers were thought to be involved in the cardiovascular and hormonal responses to long-term stress activation by environmental noises, even though the noise intensity was as low as 53 dB (23). "
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