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Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning

Identifieur interne : 001221 ( Main/Exploration ); précédent : 001220; suivant : 001222

Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning

Auteurs : Frauke Nees [Allemagne] ; Steffen Richter [Allemagne] ; Johanna Lass-Hennemann [Allemagne] ; Terry D. Blumenthal [États-Unis] ; Hartmut Sch Chinger [Allemagne]

Source :

Psychopharmacologia [ 0033-3158 ] ; 2008.

RBID : Pascal:08-0365472

Descripteurs français

Pascal (Inist)
- Inhibition, Hydrocortisone, Métyrapone, Clignement palpébral, Conditionnement classique, Processus acquisition, Système hypothalamohypophysosurrénalien, Stress, Hippocampe, Cervelet.

English descriptors

KwdEn :
- Acquisition process, Adult, Antimetabolites (pharmacology), Blinking, Cerebellum, Cerebellum (physiology), Circadian Rhythm (drug effects), Classical conditioning, Conditioning, Eyelid (drug effects), Electromyography, Female, Hippocampus, Humans, Hydrocortisone, Hydrocortisone (antagonists & inhibitors), Hydrocortisone (metabolism), Hypothalamohypophysoadrenal axis, Inhibition, Male, Metyrapone, Metyrapone (pharmacology), Patch-Clamp Techniques, Saliva (metabolism), Stress, Young Adult.
MESH :
- chemical , antagonists & inhibitors : Hydrocortisone.
- chemical , metabolism : Hydrocortisone.
- chemical , pharmacology : Antimetabolites, Metyrapone.
- drug effects : Circadian Rhythm, Conditioning, Eyelid.
- metabolism : Saliva.
- physiology : Cerebellum.
- Adult, Electromyography, Female, Humans, Male, Patch-Clamp Techniques, Young Adult.

Abstract

Rationale Hypocortisolism impairs trace classical conditioning of the eyeblink response to an air puff but does not affect delay conditioning. Objectives The opposite neurohormonal condition, hypocortisolism, may facilitate trace classical conditioning, which might be informative in understanding the role of classical conditioning in stress-sensitive syndromes such as fibromyalgia. Materials and methods Volunteers (n=82) were randomized to receive either an inhibitor of cortisol production (metyrapone, 1500 mg) or placebo and to complete a delay or a trace eyeblink conditioning protocol (unconditioned stimulus: comeal air puff, 10 psi, 50 ms; conditioned stimulus: binaural pure tone, 75 dB, 1000 Hz, 400 ms; empty interval in trace conditioning: 600 ms), where conditioned eyeblink response probability was assessed electromyographically. Results Metyrapone induced hypocortisolism, reflected by a 30% decrease of salivary cortisol levels (p<0.01), and facilitated trace eyeblink conditioning (p<0.001), while delay eyeblink conditioning remained unaffected. Moreover, extinction of delay-conditioned eyeblink responses was impaired (p=0.023), but extinction of trace-conditioned responses remained unaffected. Conclusions We conclude that acute mild metyrapone-induced hypocortisolism facilitates hippocampus-mediated classical trace eyeblink conditioning but suppresses the extinction of cerebellum-based delay-conditioned responses. Both results may be of theoretical and clinical significance for the generation and persistence of psychosomatic symptoms in patient groups characterized by relative hypocortisolism (e.g., fibromyalgia and chronic fatigue).

Affiliations:

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<term>Blinking</term>
<term>Cerebellum</term>
<term>Cerebellum (physiology)</term>
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<front><div type="abstract" xml:lang="en">Rationale Hypocortisolism impairs trace classical conditioning of the eyeblink response to an air puff but does not affect delay conditioning. Objectives The opposite neurohormonal condition, hypocortisolism, may facilitate trace classical conditioning, which might be informative in understanding the role of classical conditioning in stress-sensitive syndromes such as fibromyalgia. Materials and methods Volunteers (n=82) were randomized to receive either an inhibitor of cortisol production (metyrapone, 1500 mg) or placebo and to complete a delay or a trace eyeblink conditioning protocol (unconditioned stimulus: comeal air puff, 10 psi, 50 ms; conditioned stimulus: binaural pure tone, 75 dB, 1000 Hz, 400 ms; empty interval in trace conditioning: 600 ms), where conditioned eyeblink response probability was assessed electromyographically. Results Metyrapone induced hypocortisolism, reflected by a 30% decrease of salivary cortisol levels (p<0.01), and facilitated trace eyeblink conditioning (p<0.001), while delay eyeblink conditioning remained unaffected. Moreover, extinction of delay-conditioned eyeblink responses was impaired (p=0.023), but extinction of trace-conditioned responses remained unaffected. Conclusions We conclude that acute mild metyrapone-induced hypocortisolism facilitates hippocampus-mediated classical trace eyeblink conditioning but suppresses the extinction of cerebellum-based delay-conditioned responses. Both results may be of theoretical and clinical significance for the generation and persistence of psychosomatic symptoms in patient groups characterized by relative hypocortisolism (e.g., fibromyalgia and chronic fatigue).</div>
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Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning

Inhibition of cortisol production by metyrapone enhances trace, but not delay, eyeblink conditioning

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Abstract

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