Differential involvement of glutamatergic mechanisms in the cognitive and subjective effects of smoking.

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.

Non-cholinergic modulation of antisaccade performance: a modafinil-nicotine comparison.

INTRODUCTION: The antisaccade task provides a powerful tool with which to investigate the cognitive and neural systems underlying goal-directed behaviour, particularly in situations when the correct behavioural response requires the suppression of a prepotent response. Antisaccade errors (failures to suppress reflexive prosaccades towards sudden-onset targets) are increased in patients with damage to the dorsolateral prefrontal cortex, and in patients with schizophrenia. Nicotine has been found to improve antisaccade performance in patients with schizophrenia and healthy controls. This performance enhancing effect may be due to direct effects on the cholinergic system, but there has been no test of this hypothesis. MATERIALS AND METHODS: In a double blind, double dummy, placebo-controlled design, we compared the effect of nicotine and modafinil, a putative indirect noradrenergic agonist, on antisaccade performance in healthy non-smokers. RESULTS AND DISCUSSION: Both compounds reduced latency for correct antisaccades, although neither reduced antisaccade errors. These findings are discussed with reference to the pharmacological route of performance enhancement on the antisaccade task and current models of antisaccade performance.