1. ¹School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, UK
2. ²Department of Anatomy, Brighton & Sussex Medical School, Falmer, Brighton, BN1 9PX, UK
3. ³Brighton & Sussex University Hospitals NHS Trust, The Royal Sussex County Hospital, Eastern Road, Brighton BN2 5BE, UK
4. ⁴Department of Psychology, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK

Correspondence: Dr A Jackson, School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, UK. Tel: +44 (0)1273 642030; Fax: +44 (0)1273 642674; E-mail: aj4@bton.ac.uk

⁵These authors contributed equally to this work.

Received 9 November 2007; Revised 3 March 2008; Accepted 8 March 2008; Published online 16 April 2008.

Abstract

There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior.