Effects Of Nicotine In Smokers Research Articles

Potent Dopamine D2 Antagonists Block the Reward-Enhancing Effects of Nicotine in Smokers With Schizophrenia.

Antipsychotics that are potent dopamine (DA) D2 receptor antagonists have been linked to elevated levels of nicotine dependence in smokers with schizophrenia. Because activation of D2 receptors mediates motivation for nicotine, we examined whether potent D2 antagonists would diminish nicotine's ability to stimulate reward processing-a mechanism that may drive compensatory increases in smoking. Smokers with schizophrenia (n = 184) were recruited and stratified into medication groups based on D2 receptor antagonist potency. The effects of smoking on reward function were assessed using a probabilistic reward task (PRT), administered pre- and post-smoking. The PRT used an asymmetrical reinforcement schedule to produce a behavioral response bias, previously found to increase under conditions (including smoking) that enhance mesolimbic DA signaling. Among the 98 participants with valid PRT data and pharmacotherapy that could be stratified into D2 receptor antagonism potency, a medication × smoking × block interaction emerged (P = .005). Post-hoc tests revealed a smoking × block interaction only for those not taking potent D2 antagonists (P = .007). This group exhibited smoking-related increases in response bias (P < .001) that were absent in those taking potent D2 antagonists (P > .05). Our findings suggest that potent D2 antagonists diminish the reward-enhancing effects of nicotine in smokers with schizophrenia. This may be a mechanism implicated in the increased rate of smoking often observed in patients prescribed these medications. These findings have important clinical implications for the treatment of nicotine dependence in schizophrenia.

FKBP5 variation is associated with the acute and chronic effects of nicotine.

Stress and hormones released in response to stress influence the effects of nicotine and the severity of nicotine withdrawal. Here, we systematically examine the contribution of a stress response gene, FKBP5, to the acute and chronic behavioral effects of nicotine in smokers. Subjects were European- and African-American (EA and AA) heavy smokers who participated in an intravenous (IV) nicotine administration study (total n=169). FKBP5 rs3800373 genotype was analyzed for association to several outcomes, including nicotine withdrawal and the acute subjective, heart rate (HR), blood pressure and plasma cortisol responses to IV nicotine. Nicotine withdrawal was also examined in relation to rs3800373 allele frequencies in an independent cohort of EA and AA current smokers (n=3821). For a subset of laboratory subjects FKBP5 mRNA (n=48) expression was explored for an association to the same outcomes. The rs3800373 minor allele was associated with less severe nicotine withdrawal in laboratory subjects and the independent cohort of smokers. The rs3800373 minor allele was also associated with lower subjective ratings of negative drug effects in response to IV nicotine. Low FKBP5 mRNA expression was associated lower cortisol levels, lower subjective ratings of negative drug effects and a blunted HR response to nicotine. Stress hormone regulation via FKBP5 warrants further investigation as a potential contributor to the effects of nicotine withdrawal, which occurs commonly, and has an important role in the maintenance of smoking behavior and relapse following a quit attempt.

Nicotine modulation of information processing is not limited to input (attention) but extends to output (intention)

Nicotine influences many cognitive processes, especially those requiring high attentional loads, yet the impact of nicotine on all aspects of information processing has not been well delineated. The aim of the study was to determine the relative behavioral and functional effects of nicotine on dissociable aspects of information processing (i.e., selective attention and motor intention). Adult smokers (N = 25) and healthy controls (N = 23) performed the intention/attention task (IAT) twice, during functional magnetic resonance imaging. The IAT assesses the relative differences in performance evoked by prime stimuli that provide information regarding either the correct hand with which to respond (i.e., intentional primes) or the likely location of a target stimulus (i.e., attentional primes). Smokers were scanned 2 h after nicotine (21 mg) or placebo patch placement. The order of nicotine and placebo sessions was randomized and counter-balanced. Controls were also scanned twice, with no patch placement in either session. While drug condition had no significant effect on reaction time, smokers were overall more accurate than controls. Moreover, nicotine significantly increased the response to intentional primes in brain regions known to mediate response readiness, e.g., inferior parietal lobe, supramarginal gyrus, and striatum. While limited to participant accuracy, these data suggest that the behavioral effects of nicotine in smokers are not only limited to information processing input (i.e., selective attention) but are also generalizable to output functions (i.e., motor intention). Moreover, nicotine's effects on intention appear to be mediated by a facilitation of function in brain regions associated with information processing output.

Euphoriant effects of nicotine in smokers: fact or artifact?

The claim that nicotine in cigarettes is euphoriant to smokers is largely based on two studies (Pomerleau and Pomerleau, Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) in which smokers were instructed to respond to sensations of rush, buzz, or high while smoking low-nicotine or regular cigarettes. However, the assumption that these sensations are pleasurable was not tested and may have biased the results. The aim of this study was to re-examine the claim that smoked nicotine is euphoriant to smokers. Study 1 surveyed the frequency and pleasantness of the smoking-related sensations of rush, buzz, and high in a sample of smokers. Study 2 replicated Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992) with two sets of instruction. One set, as in the original study, defined these sensations as pleasurable, whereas the other defined them as unpleasant. Study 1 found that whereas rush and high were perceived as pleasant, buzz was unpleasant to most smokers. Study 2 found that under both sets of instructions, smokers reported more sensations when smoking the regular, as compared to the low-nicotine cigarette. Additionally, the sensations of rush, buzz, and high were rated as more pleasant under the pleasant instructions as compared to the unpleasant instructions. Finally, in the pleasant instructions condition, many participants reported having pressed the button to indicate a pleasurable sensation despite having actually experienced that sensation as unpleasant. Our results suggest that the findings of Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) may have been biased by the experimental instructions and cannot be taken as evidence that smoked nicotine is euphoriant to smokers.

Comparable Effects of Nicotine in Smokers and Nonsmokers on a Prospective Memory Task

In a double-blind placebo-controlled study, we examined the effect of nicotine, a cholinergic agonist, on performance of a prospective memory (ProM) task in young adult volunteers. Volunteers were required to complete an ongoing lexical decision task while maintaining the ProM task (responding with a different button press to items containing particular target letters). Half of the volunteers were smokers, half were nonsmokers. Half of each group received a single dose (1 mg) of nicotine nasal spray before completing the task; the remaining volunteers received a matched inactive placebo spray. Nicotine improved performance on the ProM task when volunteers were able to devote resources to that task. Under a variant procedure, where volunteers completed a concurrent auditory monitoring task, ProM performance was impaired under nicotine. Results are discussed in terms of the resource model of ProM, and the arousal model of drug effects. The data suggest that ProM under the conditions tested here is a resource-needy process, and that nicotine can improve performance by increasing available resources. Increased working memory demands that encourage redirection of resources may impair ProM performance, but the conditions under which these deficits emerge depend upon the subjective allocation of resources across tasks, rather than resource availability per se.

Authors' reply:

Authors' reply:

Contrasting renal effects of nicotine in smokers and non-smokers.

Cigarette smoking is associated with acute increase in arterial pressure due to systemic vasoconstriction and decreased skin and coronary blood flow. Virtually all cardiovascular effects of cigarette smoking are due to nicotine. However, whether nicotine also affects the renal circulation and function in humans is at present unknown. In the current study the acute effects of a 4-mg nicotine gum on arterial pressure, heart rate as well as renal haemodynamics and function were assessed in non-smokers and chronic smokers. In non-smokers, mean arterial pressure (+8 +/- 1 mmHg, P<0.001) and heart rate (+13 +/- 3 beats/min, P<0.001) increased whereas effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) decreased by 15 +/- 4% and 14 +/- 4% respectively; in addition, urinary cyclic GMP decreased by 51 +/- 12% in response to nicotine administration. In smokers, mean arterial pressure and heart rate increased similarly; however, in contrast with non-smokers, ERPF and GFR remained unchanged whereas urinary cyclic GMP rose by 87 +/- 43%. Changes in ERPF induced by nicotine were positively correlated with changes in urinary cyclic GMP. These findings indicate that nicotine administration is associated with renal vasoconstriction in healthy non-smokers, possibly through alteration of a cyclic-GMP-dependent vasoactive mechanism. Tolerance to the renal effect of nicotine was observed in chronic smokers, despite the maintenance of the systemic response to nicotine.

Behavioral performance effects of nicotine in smokers and nonsmokers

Performance on finger-tapping and handsteadiness, tasks opposite in response requirements, was compared between male smokers and nonsmokers (n = 10 each) on two occasions, once following intake of nicotine (15 μg/kg) by measured-dose nasal spray and once following placebo. Compared with nonsmokers, smokers had significantly greater increase in finger-tapping speed due to nicotine. On the other hand, smokers tended to have improved performance on handsteadiness (i.e., less involuntary movement) due to nicotine, while nonsmokers had impaired performance, although this difference was not significant. Nicotine-induced changes in performance on each task were inversely related, suggesting specificity of the behavioral effects of nicotine depending on task demands, rather than a generalized effect. These effects of nicotine on behavioral performance may be important in understanding the reinforcing value of nicotine intake, and differences in effects as a function of smoking history may suggest chronic adaptation to nicotine.

An aerosol spray alternative to cigarette smoking in the study of the behavioral and physiological effects of nicotine

For studies of the behavioral and physiological effects of nicotine in smokers, delivery of nicotine via cigarette smoking is highly variable and difficult to control. A more precise method of delivery is needed in order to accurately manipulate the amount of nicotine being presented and, thus, to determine its quantitative effects. The objective of the study reported here was to test an aerosol nasal-spray method of delivering measured doses of nicotine. Eleven healthy males were presented 0 mg (placebo), 0.5 mg, 1.0 mg, and 2.0 mg of nicotine over 5 min during four separate sessions, and changes were observed in plasma nicotine concentration and cardiovascular activity. Dose-response relationships were observed between nicotine presented via this method and plasma nicotine, heart rate, systolic blood pressure, and, to a lesser extent, diastolic blood pressure. These results suggest that this aerosol spray method of presenting nicotine provides the measured doses necessary for quantification of nicotine’s effects.