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: 7.83). 12/2007; 32(11):2405-21. DOI: 10.1038/sj.npp.1301363
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Ruihua Hou, Jun 06, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The locus coeruleus (LC) 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 review considers evidence that this sensitivity, at least to some extent, is mediated by the LC. 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. Fear-conditioning involves the association of a noxious (unconditioned) stimulus with a neutral (conditioned) stimulus (e.g., light), leading to the ability of the conditioned stimulus to evoke the "pain response". The enhancement of the startle response by conditioned fear ("fear-potentiated startle") involves the activation of the amygdala. The LC may also be involved in both sensitization and fear potentiation: pain signals activate the LC both directly and indirectly via the amygdala, which results in enhanced motoneurone activity, leading to an enhanced muscular response. Pupil diameter is under dual sympathetic/parasympathetic control, the sympathetic (noradrenergic) output dilating, and the parasympathetic (cholinergic) output constricting the pupil. The light reflex (constriction of the pupil in response to a light stimulus) operates via the parasympathetic output. The LC exerts a dual influence on pupillary control: it contributes to the sympathetic outflow 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 LC. 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 LC. It is suggested that directly applied pain and fear-conditioning may affect different populations of autonomic neurones in the LC, 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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate and to establish a model for evaluation of the instant cardiovascular responses to the noises of low-to-moderate intensity, sixteen healthy subjects were enrolled. The white noises were binaurally presented with a supra-aural earphone. The test intensities of noises were no noise, 50, 60, 70 and 80 dBA. Each noise was continued for 5 min and the electrocardiogram was simultaneously recorded. The cardiac autonomic responses were evaluated using power spectral analysis of the R-R contour obtained from digital signal processing of the ECG tracings. The result showed that the mean heart rate and mean blood pressure did not change significantly with the noises. However, the low-frequency power (LF) which represents cardiac autonomic modulations and the ratio (LHR) of LF to high-frequency power (HF) which reflects cardiac sympathetic modulations were significantly greater in the noise intensity of 50, 60, 70 and 80dBA (p<0.01, repeated measures ANOVA). In addition, the LHR was significantly correlated with the noise intensity (rho=0.90, p<0.05, Spearman's correlation analysis). The instant autonomic responses to white noises can be detected using power spectral analysis of heart rate variability and the evoked responses may provide a sensitive way to evaluate the instant effect of noise to humans.
    Autonomic neuroscience: basic & clinical 06/2010; 155(1-2):94-7. DOI:10.1016/j.autneu.2009.12.008 · 1.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Postural instability evokes cortical and autonomic reactions in addition to the primary compensatory response, and it is hypothesized that these responses may be related to underlying affective influences such as tonic physiological arousal. The purpose of this study was to determine whether perturbation-evoked cortical potentials (N1 and P2) and electrodermal responses (EDRs) were related to each other or to tonic electrodermal level (EDL). Ten healthy individuals received sixty perturbations while standing at ground level (LOW) and at the edge of an elevated platform (HIGH), where an unsuccessful reaction could lead to a fall from a height of 160 cm. Postural responses, tonic EDLs and N1 potentials were all significantly larger (p < or = 0.01) at the HIGH height relative to LOW. EDR amplitudes did not show a main effect of condition, but habituated less at the HIGH height (interaction p = 0.04). P2 potentials were not different between conditions (p > 0.05). There was no statistically significant relationship between the magnitude of change in N1 amplitude between conditions and the change in EDR amplitude between conditions (R = 0.25, p = 0.5), between magnitude of N1 change and magnitude of EDL change (R = -0.23, p = 0.25), or between magnitude of EDR change and EDL change (R = -0.51, p = 0.16). Altered cortical and autonomic responses at the HIGH height were independent of elevated physiological arousal. These findings have implications for understanding the role of cortical and autonomic responses in compensatory balance control, and alleviate concerns about the potential influence of underlying arousal on electrodermal reactivity.
    Experimental Brain Research 06/2010; 203(3):533-40. DOI:10.1007/s00221-010-2257-8 · 2.17 Impact Factor