The International Journal of Neuropsychopharmacology

Research Article

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

Boris B. Quednowa1, Philipp A. Csomora1, Joelle Chmiela1, Thilo Becka2 and Franz X. Vollenweidera1

a1 University Hospital of Psychiatry, Experimental Psychopathology and Brain Imaging, University of Zurich, Switzerland

a2 Association for Risk Reduction in Use of Drugs (ARUD), Zürich, Switzerland

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 sulphate (p.o.) at a 2-wk 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.

(Received August 24 2007)

(Reviewed October 31 2007)

(Revised November 08 2007)

(Accepted November 12 2007)

(Online publication January 16 2008)

Correspondence:

c1 Address for correspondence: B. B. Quednow, Ph.D., Dipl.-Psych., University Hospital of Psychiatry, Lenggstrasse 31, CH-8008 Zurich, Switzerland. Tel.: 0041-44-384-2777 Fax: 0041-44-384-3396 E-mail: quednow@bli.uzh.ch

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