The International Journal of Neuropsychopharmacology

Research Article

Nicotinic antagonist effects on functional attention networks

Renate Thienela1a2a3 c1, Bianca Vossa4, Thilo Kellermanna4, Martina Reskea5, Sarah Halftera4, Abigail J. Sheldricka4, Katrin Radenbacha6, Ute Habela4, Nadim Jon Shaha7, Ulrich Schalla2a3a8a9 and Tilo Kirchera10

a1 Centre for Rural and Remote Mental Health, University of Newcastle, Australia

a2 Priority Centre for Brain & Mental Health Research, University of Newcastle, Australia

a3 Schizophrenia Research Institute, Sydney, Australia

a4 Department of Psychiatry and Psychotherapy, RWTH University of Aachen, Germany

a5 Department of Psychiatry, University of California, USA

a6 Department of Psychiatry and Psychotherapy, Georg-August University of Göttingen, Germany

a7 Institute of Neuroscience and Biophysics, Research Centre Jülich GmbH, Germany

a8 Hunter Medical Research Institute, Newcastle, Australia

a9 Hunter New England Health, Newcastle, Australia

a10 Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany

Abstract

Cholinergic neurotransmission has been implicated in memory and attention. We investigated the effect of the non-competitive nicotinic antagonist mecamylamine on three components of attention processes (i.e. alerting, orienting and executive control) in 12 healthy male subjects whilst performing the Attention Network Task (ANT) in a magnetic resonance imaging (MRI) scanner. Participants received 15 mg mecamylamine in a single blind and placebo- controlled randomized procedure 90 min prior to obtaining functional MRI data. Our results confirm previous reports of beneficial effects of cueing (alerting and orienting) and detrimental effects of conflict (executive control) on reaction times when performing the ANT. The functional MRI data confirmed distinct neural networks associated with each of the three attention components. Alerting was associated with increased left temporal lobe activation while orienting increased bilateral prefrontal, right precuneus and left caudate activation. Executive control activated anterior cingulate and precuneus. Mecamylamine slowed overall response time and down-regulated brain activation associated with orienting and to some extent brain activation associated with executive control when compared to placebo. These findings are consistent with nicotinic modulation of orienting attention by cueing and executive control when responding to conflicting information. The latter nicotine antagonist effect may be mediated via cholinergic modulation of dopamine neurotransmission in mesolimbic pathways.

(Received November 24 2008)

(Reviewed December 23 2008)

(Revised June 21 2009)

(Accepted August 03 2009)

(Online publication September 09 2009)

Correspondence:

c1 Address for correspondence: Dr R. Thienel, Centre for Rural and Remote Mental Health, Locked Bag 6005, Orange, NSW 2800, Australia. Tel.: +61 2 63638457 Fax: +61 2 63612457 Email: renate.thienel@newcastle.edu.au

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