Dataset Information

Mouse model predicts effects of smoking and varenicline on event-related potentials in humans.

ABSTRACT:

Background

Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of the partial nicotine agonist varenicline on ERPs.

Methods

We measured the effects of varenicline and nicotine on the mouse P20 and varenicline and smoking on the human P50 in a paired-click task. Eighteen mice were tested following nicotine, varenicline, and their combination. One hundred and fourteen current smokers enrolled in a placebo-controlled within-subject crossover study to test the effects of varenicline during smoking and abstinence. Thirty-two subjects participated in the ERP study, with half receiving placebo first and half varenicline first (VP).

Results

Nicotine and varenicline enhanced mouse P20 amplitude, while nicotine improved P20 habituation by selectively increasing the first-click response. Similar to mice, abstinence reduced P50 habituation relative to smoking by reducing the first-click response. There was no effect of varenicline on P50 amplitude during abstinence across subjects. However, there was a significant effect of medication order on P50 amplitude during abstinence. Subjects in the PV group displayed reduced P50 during abstinence, which was blocked by varenicline. However, subjects in the VP group did not display abstinence-induced P50 reduction.

Conclusions

Data suggest that smoking improves sensory processing. Varenicline mimics amplitude changes associated with nicotine and smoking but fails to alter habituation. The effect of medication order suggests a possible carryover effect from the previous arm. This study supports the predictive validity of ERPs in mice as a marker of drug effects in human studies.

SUBMITTER: Rudnick ND

PROVIDER: S-EPMC2878727 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mouse model predicts effects of smoking and varenicline on event-related potentials in humans.

Rudnick Noam D ND Strasser Andrew A AA Phillips Jennifer M JM Jepson Christopher C Patterson Freda F Frey Joseph M JM Turetsky Bruce I BI Lerman Caryn C Siegel Steven J SJ

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20100415 6

<h4>Background</h4>Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of the partial nicotine agonist varenicline on ERPs.<h4>Methods</h4>We measured the effects of varenicline and nicotine on the mouse P20 and varenicline and smoking on the human P50 in a paired-click task. Eighteen mice were tested following nicotine, varenicline, and their combination. One hundred and fourteen curr ...[more]

PMID: 20395358

Similar Datasets

Project description:Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (??-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous ??-THC (placebo, 0.015 and 0.03?mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory 'oddball' P300 task). ??-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. ??-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, ??-THC induced psychotomimetic effects, perceptual alterations, and subjective 'high' in a dose-dependent manner. ??-THC -induced reductions in P3b amplitude correlated with ??-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to ?(9)-THC, there were no dose-related effects of ??-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, ??-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact. Collectively, the findings suggest that CB1R systems modulate top-down and bottom-up processing.

Project description:Previous research has pointed out that the combination of orthographic and semantic-associative training is a more advantageous strategy for the lexicalization of novel written word-forms than their single orthographic training. However, paradigms used previously involve explicit stimuli categorization (lexical decision), which likely influence word learning. In the present study, we used a more automatic task (silent reading) to determine the advantage of the associative training, by comparing the brain electrical signals elicited in combined (orthographic and semantic) and single (only orthographic) training conditions. In addition, the learning effect (in terms of similar neurophysiological activity between novel and known words) was also tested under a categorization paradigm, enabling determination of the possible influence of the training task in the lexicalization process. Results indicated that novel words repeatedly associated with meaningful cues showed a higher attenuation of N400 responses than those trained in the single orthographic condition, confirming the higher facilitation in the lexico-semantic processing of these stimuli, as a consequence of semantic associations. Moreover, only when the combined training was carried out in the reading task did novel words show similar N400 responses to those elicited by known words, suggesting the achievement of a similar lexical processing to known words. Crucially, when the training is carried out under a demanding task context (lexical decision), known words exhibited positive enhancement within the N400 time window, contributing to maintaining N400 differences with novel trained words and confounding the outcome of the learning. Such deflection-compatible with the modulation of the categorization-related P300 component-suggests that novel word learning could be influenced by the activation of categorization-related processes. Thus, the use of low-demand tasks arises as a more appropriate approach to study novel word learning, enabling the build-up process of mental representations, which probably depends on pure lexical and semantic factors rather than being guided by categorization demands.

Dataset Information

Mouse model predicts effects of smoking and varenicline on event-related potentials in humans.

Background

Methods

Results

Conclusions

Publications

Mouse model predicts effects of smoking and varenicline on event-related potentials in humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets