Effects of trazodone treatment on alpha-2 adrenoceptor function in depressed patients

Price, Lawrence H.; Charney, Dennis S.; Heninger, George R.

doi:10.1007/bf00175186

Cited by 20 publications

(6 citation statements)

References 65 publications

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“…The secretory pattern in demented patients with hypercortisolemia at baseline was indistinguishable from that of MDD. Clonidine decreased cortisol levels in MDD but not in normal volunteers (Siever et al, 1984); this has been attributed to an effect on alpha-2 adrenoceptors, because blockage of these receptors with yohimbine increases cortisol secretion in normal subjects (Laakmann et al, 1986) and in patients with MDD (Price, Charney, Rubin, & Heninger, 1986). The significant post-clonidine decrease in cortisol observed in the MDD group is consistent with placebo-controlled findings in another MDD sample (Siever et al, 1984) and may reflect an alpha-2 adrenoceptor effect in these subjects.…”

Section: Discussionsupporting

confidence: 71%

Clonidine Challenge of Cortisol Secretion in Dementia and Geriatric Depression

Vollhardt

Alexopoulos

Young

et al. 1989

Int. Psychogeriatr.

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The effect of oral clonidine challenge on cortisol secretion was evaluated in seven patients with primary degenerative dementia and in seven patients with major depression. Postclonidine cortisol levels were decreased in all depressed patients and in demented patients with hypercortisolemia at baseline. Demented patients with normal cortisol levels at baseline developed increased post-clonidine cortisol levels. These preliminary findings suggest differences in noradrenergic regulation of cortisol secretion among patients with primary degenerative dementia.

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Section: Discussionsupporting

confidence: 71%

Clonidine Challenge of Cortisol Secretion in Dementia and Geriatric Depression

Vollhardt

Alexopoulos

Young

et al. 1989

Int. Psychogeriatr.

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“…Although the ability of clonidine to enhance GH secretion is well established (Lal et al, 1975;Lancranjan and Marbach, 1977;Gaspar et al, 1984;Murphy et al, 1984;Hunt et al, 1986), it is recognized that there are great individual differences in the GH-secretion-stimulating effect of the drug (Lal et al, 1975;Lancranjan and Marbach, 1977;Hunt et al, 1986;Vasconcellos and Spritzer, 2004). These variations in sensitivity, coupled with inter-individual variations in the time to peak of the response (Gaspar et al, 1984;Price et al, 1986;Cavallo et al, 1990), would have militated against the detection of a more robust effect in our relatively small sample. As in the case of TSH secretion, the stimulatory effect of clonidine on GH secretion is likely to be due to the attenuation of the inhibitory influence of somatostatin on the secretion of the hormone.…”

Section: Discussionmentioning

confidence: 93%

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

Samuels

Hou

Langley

et al. 2007

Neuropsychopharmacol

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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. Keywords: acoustic startle response; auditory evoked potential; skin conductance; prepulse inhibition; clonidine; modafinil INTRODUCTIONThe startle response involves rapid involuntary contractions of facial and skeletal musculature in response to a sudden intense stimulus. In the case of the acoustic startle response, this reaction occurs in response to a sudden loud sound and is measurable in humans as an electromyographic (EMG) response from the orbicularis oculi muscle (eyeblink startle response). This response is believed to be mediated via a pathway below the level of the diencephalon consisting of between three and five central synapses, originating from the sensory receptors and terminating on the motor neurons, where the principal relay is the caudal pontine reticular nucleus (Davis et al, 1982; for review, see Yeomans and Frankland, 1996;Koch, 1999). In addition to this muscular response, changes in electroencephalographic (EEG) activity can be observed in response to the auditory stimulus, and these changes are termed auditory evoked potentials (AEP). In particular, the N1/P2 component of the AEP is measurable following the presentation of the acoustic startle stimulus (for examples, see Abduljawad et al, 1999Abduljawad et al, , 2001 Phillips et al, 2000a, b;Graham et al, 2001Graham et al, , 2004Scaife et al, 2005Scaife et al, , 2006. Both the muscular and the AEP responses are fast responses; longer-latency responding to the startle stimulus can be observed in autonomic activity, in particular in sympathetically mediated skin conductance...

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“…The specific effect of guanfacine on the response bias for sad faces suggests an application for α 2 adrenoceptor agonists in the treatment of the mood-congruent biases that characterize major depression (Blaney 1986). However, α 2 adrenoceptor agonists have no reported antidepressant properties, and successful antidepressant treatment does not seem to involve alterations of adrenoceptor function (Charney et al 1984; Price et al 1986). The lack of antidepressant effects may in part reflect the selective action of guanfacine on executive functions mediated by DLPFC (Jakala et al 1999), rather than on the limbic affective mechanisms that have been implicated in both mood-congruent biases (Elliott et al 2000, 2002) and the pathophysiology of major depression (Elliott et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control

et al. 2012

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Rationale Functional interactions between limbic regions that process emotions and frontal networks that guide response functions provide a substrate for emotional cues to influence behavior. Stimulation of postsynaptic α2 adrenoceptors enhances the function of prefrontal regions in these networks. However, the impact of this stimulation on the emotional biasing of behavior has not been established. Objectives This study tested the effect of the postsynaptic α2 adrenoceptor agonist guanfacine on the emotional biasing of response execution and inhibition in prefrontal cortex. Methods Fifteen healthy young adults were scanned twice with functional magnetic resonance imaging while performing a face emotion go/no-go task following counterbalanced administration of single doses of oral guanfacine (1 mg) and placebo in a double-blind, crossover design. Results Lower perceptual sensitivity and less response bias for sad faces resulted in fewer correct responses compared to happy and neutral faces, but had no effect on correct inhibitions. Guanfacine increased the sensitivity and bias selectively for sad faces, resulting in response accuracy comparable to happy and neutral faces, and reversed the valence-dependent variation in response-related activation in left dorsolateral prefrontal cortex (DLPFC), resulting in enhanced activation for response execution cued by sad faces relative to happy and neutral faces, in line with other frontoparietal regions. Conclusions These results provide evidence that guanfacine stimulation of postsynaptic α2 adrenoceptors moderates DLPFC activation associated with the emotional biasing of response execution processes. The findings have implications for the α2 adrenoceptor agonist treatment of attention-deficit hyperactivity disorder (ADHD).

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Effects of trazodone treatment on alpha-2 adrenoceptor function in depressed patients

Cited by 20 publications

References 65 publications

Clonidine Challenge of Cortisol Secretion in Dementia and Geriatric Depression

Clonidine Challenge of Cortisol Secretion in Dementia and Geriatric Depression

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

Guanfacine modulates the influence of emotional cues on prefrontal cortex activation for cognitive control

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