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Sensorimotor gating and attentional set-shifting are improved by the μ-opioid receptor agonist morphine in healthy human volunteers


Quednow, B B; Csomor, P A; Chmiel, J; Beck, T; Vollenweider, F X (2008). Sensorimotor gating and attentional set-shifting are improved by the μ-opioid receptor agonist morphine in healthy human volunteers. International Journal of Neuropsychopharmacology, 11:655-669.

Abstract

Prepulse inhibition (PPI) of the acoustic startle response (ASR) has been established as an operational measure of sensorimotor gating. Animal and human studies have shown that PPI can be modulated by dopaminergic, serotonergic, and glutamatergic drugs and consequently it was proposed that impaired sensorimotor gating in schizophrenia parallels a central abnormality within the corresponding neurotransmitter systems. Recent animal studies suggest that the opioid system may also play a role in the modulation of sensorimotor gating. Thus, the present study investigated the influence of the μ-opioid receptor agonist morphine on PPI in healthy human volunteers.
Eighteen male, non-smoking healthy volunteers each received placebo or 10 mg morphine sulfate (p.o.) at a two week interval in a double-blind, randomized, and counterbalanced order. PPI was measured 75 min after drug/placebo intake. The effects of morphine on mood were measured by the Adjective Mood Rating Scale and side effects were assessed by the List of Complaints. Additionally, we administered a comprehensive neuropsychological test battery consisting of tests of the Cambridge Neuropsychological Test Automated Battery and the Rey Auditory Verbal Learning Test.
Morphine significantly increased PPI without affecting startle reactivity or habituation. Furthermore, morphine selectively improved the error-rate in an attentional set-shifting task but did not influence vigilance, memory, or executive functions.
These results imply that the opioid system is involved in the modulation of PPI and attentional set-shifting in humans and they raise the question whether the opioid system plays a crucial role also in the regulation of PPI and attentional set-shifting in schizophrenia.

Prepulse inhibition (PPI) of the acoustic startle response (ASR) has been established as an operational measure of sensorimotor gating. Animal and human studies have shown that PPI can be modulated by dopaminergic, serotonergic, and glutamatergic drugs and consequently it was proposed that impaired sensorimotor gating in schizophrenia parallels a central abnormality within the corresponding neurotransmitter systems. Recent animal studies suggest that the opioid system may also play a role in the modulation of sensorimotor gating. Thus, the present study investigated the influence of the μ-opioid receptor agonist morphine on PPI in healthy human volunteers.
Eighteen male, non-smoking healthy volunteers each received placebo or 10 mg morphine sulfate (p.o.) at a two week interval in a double-blind, randomized, and counterbalanced order. PPI was measured 75 min after drug/placebo intake. The effects of morphine on mood were measured by the Adjective Mood Rating Scale and side effects were assessed by the List of Complaints. Additionally, we administered a comprehensive neuropsychological test battery consisting of tests of the Cambridge Neuropsychological Test Automated Battery and the Rey Auditory Verbal Learning Test.
Morphine significantly increased PPI without affecting startle reactivity or habituation. Furthermore, morphine selectively improved the error-rate in an attentional set-shifting task but did not influence vigilance, memory, or executive functions.
These results imply that the opioid system is involved in the modulation of PPI and attentional set-shifting in humans and they raise the question whether the opioid system plays a crucial role also in the regulation of PPI and attentional set-shifting in schizophrenia.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:August 2008
Deposited On:25 Aug 2008 10:46
Last Modified:05 Apr 2016 12:26
Publisher:Cambridge University Press
ISSN:1461-1457
Publisher DOI:10.1017/S1461145707008322
PubMed ID: 18272020
Permanent URL: http://doi.org/10.5167/uzh-3304

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