Nicotine-specific and non-specific effects of cigarette smoking on endogenous opioid mechanisms.

This study investigates differences in μ-opioid receptor mediated neurotransmission in healthy controls and overnight-abstinent smokers, and potential effects of the OPRM1 A118G genotype. It also examines the effects of smoking denicotinized (DN) and average nicotine (N) cigarettes on the μ-opioid system. Positron emission tomography with (11)C-carfentanil was used to determine regional brain μ-opioid receptor (MOR) availability (non-displaceable binding potential, BPND) in a sample of 19 male smokers and 22 nonsmoking control subjects.

Regional brain [(11)C]carfentanil binding following tobacco smoking.

Objective: To determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco smoking.

Methods: Twenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [(11)C]carfentanil.

Tobacco smoking produces greater striatal dopamine release in G-allele carriers with mu opioid receptor A118G polymorphism.

Objective: To determine if carriers of the allelic expression of the G variant of the human mu opioid receptor (OPRM1) A118G polymorphism have greater increases in striatal dopamine (DA) release after tobacco smoking.

Methods: Nineteen of 20 genotyped male tobacco smokers, after overnight abstinence, smoked denicotinized (denic) and average nicotine (nic) containing tobacco cigarettes in a PET brain imaging study using [(11)C]raclopride.

Results: The right striatum had more free D(2) receptors than the left striatum pre- and post-tobacco smoking.

Denicotinized versus average nicotine tobacco cigarette smoking differentially releases striatal dopamine.

Introduction: Nicotine has long been recognized as a necessary but insufficient component of tobacco cigarettes to maintain a psychophysiological need to smoke. This study examined venous plasma concentrations effects of nicotine in cigarette smoking after overnight abstinence to release striatal dopamine (DA).

Methods: Twenty-two male smokers smoked either denicotinized (denic) or average nicotine (nic) cigarettes under single blind conditions.

Venous plasma nicotine correlates of hormonal effects of tobacco smoking.

The present study resolves some of the discrepancies in the literature by correlating the effects of tobacco smoking on hormone release with venous plasma nicotine levels. Cortisol, prolactin, and beta-endorphin concentrations were measured. Habitual male tobacco users smoked denicotinized (very low nicotine) and average nicotine cigarettes in the morning after overnight tobacco abstinence.

Tobacco smoking produces widespread dominant brain wave alpha frequency increases.

The major pharmacological ingredient in tobacco smoke is nicotine, a mild stimulant known to alter brain electrical activity. The objective of this study was to determine if tobacco smoking in humans produces localized or widespread neocortical dominant alpha electroencephalographic (EEG) frequency increases consistent with nicotine stimulation of the brainstem activating system in animals. Twenty-two male volunteer non-deprived tobacco smokers were studied.

Biperiden enhances L-DOPA methyl ester and dopamine D(l) receptor agonist SKF-82958 but antagonizes D(2)/D(3) receptor agonist rotigotine antihemiparkinsonian actions.

The effects of biperiden (0, 100, and 320 microg/kg), a selective muscarinic M(1)/M(4) receptor cholinergic antagonist, were studied alone and in combination with those of L-DOPA methyl ester (16.7 mg/kg), a selective dopamine D(1) receptor agonist SKF-82958 (74.8 microg/kg), or a selective D(2)/D(3) receptor agonist rotigotine (32 microg/kg) on circling behavior in MPTP induced hemiparkinsonian monkeys.

Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans.

This is a pilot examination of the hypothesis that some of the effects of smoking cigarettes in humans are mediated through nicotine activation of opioid and dopamine (DA) neurotransmission. Neuroimaging was performed using positron emission tomography and the radiotracers [11C]carfentanil and [11C]raclopride, labeling mu-opioid and DA D2 receptors, respectively. Six healthy male smokers were abstinent overnight.

Regional cerebral blood flow responses to smoking in tobacco smokers after overnight abstinence.

Objective: The purpose of the study was to determine the effects of cigarette smoking on brain regional function in a group of chronic smokers by using cerebral blood flow (CBF) measures and positron emission tomography (PET).

Method: Nineteen tobacco smokers were studied after about 12 hours of smoking abstinence. Regional CBF (rCBF) measures were obtained with PET and [15O]H2O in six consecutive scans.

Changes in craving for a cigarette and arterial nicotine plasma concentrations in abstinent smokers.

Although the relationship between nicotine and changes in heart rate and blood pressure has been demonstrated, the relationship between nicotine and subjective effects such as decreased craving, relaxation, sickness, and decreased nervousness, is less well delineated. In this study, arterial nicotine levels were drawn in 21 smokers who smoked two average nicotine (AN) cigarettes and one low nicotine (LN) cigarette. Craving for a cigarette, relaxation, sickness, and decreased nervousness were rated on a visual analog scale (VAS) before and after smoking each cigarette.

Regional cerebral blood flow and plasma nicotine after smoking tobacco cigarettes.

The hypothesis for this research is that only in some brain areas, regional cerebral blood flow (rCBF) after tobacco smoking is correlated with arterial plasma nicotine concentrations. Twenty-one healthy adult tobacco smokers of both genders were studied after overnight tobacco abstinence. H(2)15O water was used to measure rCBF.

Effects of (+/-)-idazoxan alone and in combination with L-DOPA methyl ester in MPTP-induced hemiparkinsonian monkeys.

The effects of a combination of the alpha2-adrenergic receptor antagonist (+/-)-idazoxan with L-DOPA methyl ester were examined in three of four female adult monkeys (Macaca nemestrina) rendered hemiparkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). (+/-)-Idazoxan (0.16, 0.

Comparative American and Japanese tobacco smoke uptake parameters after overnight tobacco deprivation.

American and Japanese overnight deprived tobacco smokers were compared with respect to expired CO, plasma nicotine and cotinine, and red cell carboxyhemoglobin. The participants were 51 of 59 American and 55 of 86 Japanese cigarette smokers of mixed gender who met similar strict criteria. Female and male American tobacco smokers were similar in mean age, number of cigarettes smoked per day, machine-rated nicotine and tar yield per cigarette and per 24 h plasma cotinine, calculated previous 24 h nicotine dose, and exhaled CO.

Clinical phenotyping strategies in selection of tobacco smokers for future genotyping studies.

Various behavioral and chemical measures were studied as potential simplified phenotyping techniques in overnight abstinent tobacco smokers. Irrespective of the machine-rated nicotine delivery (yield) of the cigarette used, there was a statistically significant correlation between the number of cigarettes consumed per day and overnight abstinence plasma cotinine concentration (r=.88) and its calculated nicotine dose per day (r=.

Comparative effects of tobacco smoking and nasal nicotine.

Objective: Compare the electroencephalographic (EEG) and cardiovascular effects of tobacco smoking and nasal nicotine in the same subjects.

Methods: Eleven volunteer smokers were studied after >10 h of overnight tobacco deprivation. Quantitative EEG was used to measure brain electrical changes produced by four different treatments.