Vadim Ilivitsky

Transdermal Nicotine: Single Dose Effects on Mood, EEG, Performance, and Event-Related Potentials

A 21-mg dose of nicotine was administered transdermally to 16 overnight smoking-deprived smokers in a double-blind, placebo-controlled design. Mood ratings, electroencephalography (EEG), behavioral performance and event-related potential (ERP: P300) indices of attention and information processing speed were assessed before and 4 h after placebo/nicotine treatment. Although nicotine, relative to placebo, failed to alter mood, it increased absolute and relative power indices of EEG arousal, shortened reaction times, and increased P300 amplitudes. The results are discussed in relation to nicotines actions on cholinergic transmission and its role in smoking behavior.

Acute nicotine effects on auditory sensory memory in tacrine-treated and nontreated patients with Alzheimer's disease: an event-related potential study.

The auditory mismatch negativity (MMN) event-related brain potential (ERP) reflects the storage of information in acoustic sensory memory. Thirteen patients with Alzheimers disease (AD), 6 receiving treatment with the cholinesterase inhibitor, tacrine [tetrahydroaminoacridine (THA)], and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and placebo. MMNs were recorded with 1- and 3-s interstimulus intervals (ISIs) during pre- and post-placebo/nicotine administration. Amplitudes decreased from pre- to post-placebo recordings in nontreated patients but remained stable in THA-treated patients. Comparison of pre- and post-nicotine MMNs found amplitude increases with nicotine in nontreated but not in THA-treated patients. MMN latencies were shortened by nicotine in both treatment groups. These exploratory findings suggest that nicotine-improved strength of acoustic sensory memory traces and speed of acoustic sensory discrimination in AD are differentially affected by chronic tacrine treatment.

The Cholinergic Basis of the Smoking-Induced EEG Activation Profile

Acute quantitative electroencephalographic effects of cigarette smoking were examined in 15 smokers within a repeated-measures design which assessed changes in power-spectral estimates following acute pre-treatment with placebo, a dose (20 mg) of mecamylamine, a dose (0.6 mg) of scopolamine and a combined dose of mecamylamine and scopolamine. Compared to sham smoking, the smoking of a single cigarette following placebo pre-treatment reduced absolute and relative power in slow (delta, theta) frequency bands, increased absolute and relative power in alpha and beta frequency bands and accelerated mean frequency. These smoking-induced power changes in slow- and fast-frequency bands were differentially affected by the separate and combined actions of the cholinergic antagonists with treatments involving mecamylamine tending to abolish smoking-induced slow-frequency absolute power reductions and fast-frequency relative power increments. Self-ratings of smoking-induced increases in alertness were altered by mecamylamine and combined treatments while sensory aspects of cigarette smoking were only altered with combined mecamylamine and scopolamine pre-treatment. The results are discussed with respect to brain-behaviour relationships and mechanisms maintaining the smoking habit.

Nicotine and smoker status moderate brain electric and mood activation induced by ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist

As the increased smoking prevalence in schizophrenics may be interpreted as an adaptive response to an underlying biological defect, investigations into nicotines actions within N-methyl-d-aspartate (NMDA) antagonist drug models of schizophrenia may improve our understanding of the role of glutamatergic neurotransmission in initiating and maintaining nicotine dependence in this disorder. In this double-blind, placebo-controlled, randomized study, the electroencephalographic (EEG) and subjective response to a sub-psychotomimetic intravenous dose of the NMDA antagonist ketamine was examined in 20 regular smokers and 20 non-smokers pretreated with placebo or nicotine gum. Although nicotine increased EEG arousal, ketamine produced electrocerebral signs of brain activation (decreased slow wave power) and sedation (decreased fast wave power and frequency), which were not affected by nicotine pretreatment and were evident only in non-smokers. Ketamine increased a number of self-report indices of subjective arousal, some of which were attenuated and potentiated by nicotine in smokers and non-smokers, respectively. These findings suggest that long-term (evidenced by smoker vs. non-smoker comparisons) and short-term (acute) nicotine exposure may alter NMDA receptor-mediated arousal and mood systems in a way that promotes nicotine dependence in smokers, and addresses neurobiological deficiencies in smokers with schizophrenia.

Effects of Acute Nicotine Administration on Cognitive Event-Related Potentials in Tacrine-Treated and Non-Treated Patients with Alzheimer’s Disease

Earlier studies of cognitive event-related brain potentials (ERPs) reporting diminished amplitudes and delayed latencies of the P300 potential in dementia of the Alzheimer type (DAT), together with independent findings of the P300- and performance-enhancing properties of nicotine in normal adults, stimulated this study to explore the single-dose effects of nicotine on auditory and visual P300s in DAT. Thirteen patients, 6 currently receiving treatment with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining being medication free, were administered 2 mg of nicotine polacrilex under double-blind, randomized, placebo-controlled conditions. Prior to nicotine administration, THA-treated patients exhibited shorter auditory P300 latencies than non-treated patients. Acutely administered nicotine failed to alter auditory P300, but increased the amplitudes of visual P300s in both DAT patient groups. Neither THA treatment nor single-dose nicotine altered behavioural performance in the visual and auditory task paradigms. The results are discussed in relation to nicotinic cholinergic, attentional and cognitive processes in DAT.

Acute nicotine administration in Alzheimer's disease: an exploratory EEG study.

Previous findings of cognitive deficits and EEG slowing in Alheimer’s patients, together with independent reports of the performance enhancing and electrocortical activating properties of nicotine in normal adults, stimulated this study to examine the acute effects of nicotine on spectrum-analyzed EEG in patients with dementia of the Alzheimer type (DAT). Thirteen patients, 6 currently receiving cholinesterase inhibitor treatment and the remaining being medication free, were administered 2 mg of nicotine polacrilex under randomized, placebo-controlled conditions. Compared to age-regressed EEG norms, the pretreatment EEG spectrums of patients in general were characterized by excessive slow (delta and theta)-wave power, diminished fast (alpha and beta)-wave power and slow mean alpha and total band frequencies. Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power. No differences were observed between treated and nontreated patients in response to nicotine. The results are discussed in relation to cholinergic and brain arousal systems and their relationship to cognitive processes.

Clonidine pre-treatment fails to block acute smoking-induced EEG arousal/mood in cigarette smokers

Given the arousal eliciting actions of smoking and nicotine, and the contributing role of noradrenaline in brain arousal systems, this study examined the neuroelectric and affective correlates of cigarette smoking following acute pre-treatment with the alpha 2-noradrenergic auto-receptor agonist, clonidine. In a double-blind placebo-controlled crossover design, quantitative electroencephalography (EEG), mood, and smoking withdrawal symptoms were assessed in 12 overnight smoking abstinence smokers, before and after sham and cigarette smoking. Orally administered clonidine (0.1 mg) failed to alter overnight smoking abstinence symptoms or the EEG arousal and mood-elevating response seen with the smoking of a single cigarette. The results are discussed in relation to neural mechanisms underlying the acute reinforcement maintaining nicotine use.

Effects of tryptophan depletion on acute smoking abstinence symptoms and the acute smoking response

Given the putative role of serotonin in the modulation of smoking withdrawal and the central actions of nicotine, this study examined the affective and neuroelectric correlates of smoking abstinence and cigarette smoking following depletion of the serotonin precursor, tryptophan. In a randomized, double-blind two session (tryptophan depletion [TD] vs. nondepletion), placebo-controlled design, spectrally analyzed electroencephalogram (EEG), self-ratings of withdrawal symptoms and mood states were assessed in 18 male cigarette smokers before smoking abstinence, 5 h postsmoking abstinence and again following sham smoking and the smoking of one cigarette. Compared to a nutritionally balanced amino acid (AA) mixture containing tryptophan (i.e., placebo mixture), oral ingestion of a similar mixture devoid of tryptophan resulted in a 70% reduction of plasma tryptophan but failed to alter the appearance or reversal (by acute cigarette smoking) of withdrawal symptoms, negative mood states and increased slow wave EEG in male smokers deprived of cigarettes. These results, although not supporting a role for the serotonergic system in acute smoking and early smoking abstinence symptoms, are discussed in relation to the neuropharmacology of smoking behavior and suggestions for future work.

Effects of Haloperidol Pretreatment on the Smoking-Induced EEG/Mood Activation Response Profile

This study examined the role of dopamine in modulating the CNS response to cigarette smoking. In a randomized, double-blind, repeated-measures design, quantitative electroencephalographic (EEG) changes and self-reports induced by the smoking of a single cigarette were assessed in 16 smokers following pretreatment with placebo and a dopamine antagonist, haloperidol (2 mg). Following placebo pretreatment, absolute (µV) and relative (%) amplitudes in slow-frequency bands (δ, Θ, α1) were reduced and absolute and relative amplitudes in fast-frequency bands (α2, β) were increased following cigarette smoking as compared to sham smoking. Haloperidol pretreatment inhibited the smoking-induced increase in absolute β frequency. Self-ratings indicated that cigarette smoking induced increases in alertness, contentedness and calmness but not euphoria, and reduced cigarette cravings as compared to the sham smoking conditions. Smoking-induced, α2 increments were associated with increases in alertness and decreases in euphoria while β increments were associated with increased calmness. Smoking-related self-ratings of mood and cigarette acceptability were not altered by haloperidol, but subjects were less content overall in the haloperidol condition as compared to placebo. Discussion of these results focuses on transmitter systems and their relationship to neuro-electric and behavioural activities associated with the smoking habit.

Electrocortical effects of acute tryptophan depletion on emotive facial processing in depression-prone individuals

This study assessed the effects of acute tryptophan depletion (ATD), which transiently lowers CNS 5-HT, on electrocortical responses to facial expression processing in individuals with a family history of depression (FH+). Electroencephalograph (EEG)-derived event-related potentials (ERPs) were acquired from 18 FH+ individuals during a facial expression recognition task (neutral and sad, joy and surprise at 50% and 100% intensities). Both early positive (P1 and P2) and the face-specific N170 ERP components were differentially altered by emotional intensity and valence. Increased depression, confusion and total mood disturbance scores, and decreased calmness, were observed with ATD (versus placebo). ATD was also associated with enhanced P1 and P2 amplitudes for sad versus joyful expressions. The N170 was not modulated by treatment, but was affected by emotive valence. Therefore, ATD enhanced ERP-indexed early processing of sad facial expressions, and altered the processing of positive ones, in FH+ individuals.