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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    ABSTRACT: Chronic exposure to musical auditory stimulation has been reported to improve cardiac autonomic regulation. However, it is not clear if music acutely influences it in response to autonomic tests. We evaluated the acute effects of music on heart rate variability (HRV) responses to the postural change maneuver (PCM) in women. We evaluated 12 healthy women between 18 and 28 years old and HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains. In the control protocol, the women remained at seated rest for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. In the music protocol, the women remained at seated rest for 10 minutes, were exposed to music for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. HRV was recorded at the following time: rest, music (music protocol) 0--5, 5--10 and 10--15 min during standing. In the control protocol the SDNN, RMSSD and pNN50indexes were reduced at 10--15 minutes after the volunteers stood up, while the LF (nu) index was increased at the same moment compared to seated rest. In the protocol with music, the indexes were not different from control but the RMSSD, pNN50 and LF (nu) were different from the music period. Musical auditory stimulation attenuates the cardiac autonomic responses to the PCM.
    International Archives of Medicine 08/2013; 6(1):32. DOI:10.1186/1755-7682-6-32 · 1.08 Impact Factor
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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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    ABSTRACT: The locus coeruleus is activated by noxious stimuli, and this activation leads to inhibition of perceived pain. As two physiological reflexes, the acoustic startle reflex and the pupillary light reflex, are sensitive to noxious stimuli, this sensitivity, at least to some extent, may be mediated by the locus coeruleus. The acoustic startle reflex, contraction of a large body of skeletal muscles in response to a sudden loud acoustic stimulus, can be enhanced by both directly (“sensitization”) and indirectly (“fear conditioning”) applied noxious stimuli. The enhancement of the startle response by conditioned fear (“fear-potentiated startle”) involves the activation of the amygdala. The locus coeruleus may also be involved in both sensitization and fear potentiation: pain signals activate the locus coeruleus both directly and indirectly via the amygdala, which results in enhanced motoneurone activity, leading to an enhanced muscular response. The light reflex response is constriction of the pupil evoked by a light stimulus. The pupil is dilated by the sympathetic and constricted by the parasympathetic output to the iris. The locus coeruleus contributes to the sympathetic outflow to the iris and attenuates the parasympathetic output by inhibiting the Edinger-Westphal nucleus, the preganglionic cholinergic nucleus in the light reflex pathway. Noxious stimulation results in pupil dilation (“reflex dilation”), without any change in the light reflex response, consistent with sympathetic activation via the locus coeruleus. Conditioned fear, on the other hand, results in the attenuation of the light reflex response (“fear-inhibited light reflex”), consistent with the inhibition of the parasympathetic light reflex via the locus coeruleus. Directly applied pain and fear conditioning may affect different populations of autonomic neurones in the locus coeruleus, directly applied pain activating sympathetic and fear conditioning parasympathetic premotor neurones.
    Frontiers in Integrative Neuroscience 10/2012; 6:94. DOI:10.3389/fnint.2012.00094
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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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    ABSTRACT: Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: "auditory stimulation", "autonomic nervous system", "music" and "heart rate variability". The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders.
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