Drug effects: Agonistic and antagonistic processes

Flaten, Magne Arve

doi:10.1111/j.1467-9450.2009.00776.x

Cited by 11 publications

(9 citation statements)

References 45 publications

(74 reference statements)

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“…This interpretation concurs with findings by Flaten et al (), who reported a drug‐antagonistic conditioned response in a pharmacological conditioning paradigm using a muscle relaxant to decrease blink reflex amplitude and duration in healthy volunteers. It also corresponds with earlier reviews on drug conditioning paradigms (Eikelboom & Stewart, ; Flaten, ; Ramsay & Woods, ) postulating that CS exposure may generate physiological responses that resemble the observed drug effect (agonistic response) or in a direction opposite to that of the observed drug effect (antagonistic response) in activating homeostatic mechanisms (Flaten, ). (4) Since this is the first attempt to examine conditioning changes in sleep architecture, it is possible that amitriptyline‐induced REM sleep suppression is not susceptible to behavioral conditioning.…”

Section: Discussionsupporting

confidence: 87%

“…At the same time, research on the phenomenon of drug habituation (Flaten, Simonsen, Waterloo, & Olsen, ) indicates that drug tolerance could be explained by a drug‐antagonistic conditioned response (in terms of the body's way of preparing for the effects of the drug) inhibiting the drug effect. Thus, in some cases the conditioned response mimics the observed drug effect and in others it appears in a direction opposite to that of the observed drug effect (Eikelboom & Stewart, ; Flaten, ).…”

mentioning

confidence: 97%

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Conditioning of amitriptyline‐induced REM sleep suppression in healthy participants: A randomized controlled trial

et al. 2016

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Clinical trials in sleep disorders report substantial improvement in symptoms in their placebo groups. Behavioral conditioning is one of the underlying mechanisms of the placebo response. However, we do not know whether, and if so, the extent to which sleep architecture is influenced by behavioral conditioning, similarly to other physiological responses (i.e., those in the immune system). We therefore applied a conditioning paradigm to 39 healthy adults pairing a novel-tasting drink (conditioned stimulus, CS) with the REM sleep suppressing tricyclic antidepressant amitriptyline as unconditioned stimulus during the acquisition phase. Subsequent sole presentation of the CS (together with a placebo pill) in an evocation night led to significantly more REM sleep in the amitriptyline group. Instead of the expected REM sleep suppression in the evocation night, we observed more REM sleep, indicating a rebound that interferes with the conditioned response.

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 97%

Conditioning of amitriptyline‐induced REM sleep suppression in healthy participants: A randomized controlled trial

et al. 2016

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“…Conditioned responses to drugs as USs are not only compensatory or antagonistic physiological responses (Siegel, 2008). When drugs restore homeostasis, e.g., reduction of pain, an agonistic placebo conditioned response can be observed (Flaten, 2009). …”

Section: Psychological Mechanisms Of the Placebo Effect: Contributionmentioning

confidence: 99%

The Placebo Effect: Advances from Different Methodological Approaches

Meißner¹,

Bingel²,

Colloca³

et al. 2011

J. Neurosci.

148

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There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.

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“…The decreasing likelihood of response in subsequent trials raises the possibility that in some patients, response to pharmacologic agents may be subject to learning effects including sensitization, habituation, and classical conditioning effects [3][4][5][6]. Repeated exposure to antidepressant medication may constitute a conditioning procedure wherein cues in the treatment environment including the act of pill taking become conditioned stimuli ('CSs') due to their pairing with the physiologic effect of drug (the unconditioned stimulus or 'US').…”

Section: Introductionmentioning

confidence: 99%

Neurophysiologic effects of repeated exposure to antidepressant medication: Are brain functional changes during antidepressant administration influenced by learning processes?

et al. 2013

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a b s t r a c tMajor Depressive Disorder (MDD) is a lifelong and recurrent illness, such that many individuals require multiple courses of antidepressant medication treatment. While some patients respond completely to each course of treatment, many do not, and with each unsuccessful antidepressant trial the likelihood that a patient will respond decreases. This raises the possibility that neurophysiologic response in subsequent antidepressant treatment may be influenced by learning processes including sensitization, habituation, and/or classical conditioning. Classical conditioning would entail the association of cues such as pill-taking (conditioned stimuli; CS) with the effects of active medication (unconditioned stimulus; US), such that later presentation of the CS alone would come to elicit a conditioned response (CR). Such effects could be revealed by blinded administration of placebo following a period of treatment with active medication. Habituation effects (tolerance), or sensitization effects (increased response), which require only repeated exposure to a stimulus, might be evidenced after repeated courses of antidepressant treatment. Knowledge of how learning processes impact neurophysiologic response to successive courses of antidepressant treatment would have relevance for clinical populations. Specific hypotheses, however, may be tested in healthy non-clinical samples to avoid potential confounding factors related to severity or chronicity of illness. Learning theories would suggest two hypotheses: (1) neurophysiologic response to placebo will differ between subjects who were previously treated with antidepressant treatment as compared to placebo (classical conditioning hypothesis); and (2) neurophysiologic response to an initial course of antidepressant treatment will differ from response to a repeated course of antidepressant treatment. Pilot data addressed these hypotheses in healthy never-depressed women who had previously received four weeks of venlafaxine IR, 150 mg (antidepressant-experienced subjects; n = 2) or matching placebo (antidepressant-naive subjects; n = 4) under double-blind conditions. Six-and-a-half years later, we treated these six women with placebo for one week, followed by four weeks of double-blind treatment with venlafaxine IR, 150 mg. Brain functional changes over the course of treatment were assessed using quantitative electroencephalography (qEEG) to compare prefrontal neurophysiologic responses between subjects who had, versus had not, previously been exposed to venlafaxine. Antidepressant-experienced versus antidepressant-naive subjects showed greater decreases in prefrontal cordance (PFC) during venlafaxine administration (sensitization hypothesis) but did not show significantly different PFC changes during treatment with placebo in this small pilot sample (classical conditioning hypothesis). Data suggest that brief treatment with antidepressant medication may have an enduring impact on neurophysiologic responses to a subsequent course of antidepressant treatment. Hyp...

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Drug effects: Agonistic and antagonistic processes

Cited by 11 publications

References 45 publications

Conditioning of amitriptyline‐induced REM sleep suppression in healthy participants: A randomized controlled trial

Conditioning of amitriptyline‐induced REM sleep suppression in healthy participants: A randomized controlled trial

The Placebo Effect: Advances from Different Methodological Approaches

Neurophysiologic effects of repeated exposure to antidepressant medication: Are brain functional changes during antidepressant administration influenced by learning processes?

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