Increased serotonin receptor density and platelet GPIIb/IIIa activation among smokers.

This study sought to determine whether depressive symptoms and/or platelet serotonin receptor (5HT2A) density are associated with increased platelet activation (PA) found among smokers. Flow cytometric detection of PA was used to study 36 smokers and 16 nonsmokers, aged 18 to 48 years. Subjects were tested at baseline and after either smoking 2 cigarettes (smokers) or a similar resting interval (nonsmokers). Assessment of PA included both platelet secretion and fibrinogen receptor (GPIIb/IIIa) binding. Platelet 5HT2A receptor binding and saturation were tested using [3H]LSD, and depressive symptoms were measured using the Beck Depression Inventory. Platelet 5HT2A receptor density was increased among smokers versus nonsmokers (82.7+/-67.7 versus 40.0+/-20.2 fmol/mg protein; P<0.005), and there was a dose-dependent relationship between receptor density and packs/d among smokers. Baseline wound-induced GPIIb/IIIa binding at 1 minute and GPIIb/IIIa binding in response to collagen stimulation in vitro was increased among smokers (P<0.05); there were no changes in PA among smokers after smoking, and platelet secretion was not elevated among smokers. Depressive symptoms were associated with 5HT2A receptor density among nonsmokers (P<0.005), but no such relationship was evident among smokers; PA was unrelated to 5HT2A receptor density in either group. The findings indicate that smoking is associated with increased platelet serotonin receptor density and with increased GPIIb/IIIa receptor binding, although these 2 factors are not related to each other or to depressive symptoms among smokers. Serotonergic dysfunction may be an important factor in the development of cardiovascular disease among smokers.

Effects of stress on circulating nicotine and cotinine levels and in vitro nicotine metabolism in the rat.

The effects of physical and psychological stress on circulating nicotine levels and conversion of nicotine to cotinine were examined in the rat. Animals received one of three dosages of nicotine (0, 6, and 12 mg/kg) via miniosmotic pumps. On day 14 of drug infusion, animals from each drug condition were randomly assigned to one of three stress conditions (noise, rubber ligature, or no stress). After 2.5 h of stress exposure, animals were killed and plasma nicotine and cotinine were measured in vivo and hepatic conversion of nicotine to cotinine was determined in vitro. Stress lowered blood nicotine levels. However, this difference was statistically significant only among animals receiving 12 mg/kg per day nicotine. In contrast, stress had no consistent effect on either measure of conversion of nicotine to cotinine in rats. Taken together, these results suggest that stress lowers circulating nicotine levels. However, the mechanism by which this occurs remains unclear.

Acute administration of phenylpropanolamine fails to affect resting energy expenditure in men of normal weight.

Studies have consistently found that dieters using over-the-counter weight control products containing phenylpropanolamine (PPA) are more successful at losing weight than those who do not. To explore the possibility that drug-induced metabolic changes contribute to weight loss associated with this compound, this study investigated the effects of PPA on resting metabolic rate in 20 healthy men of normal weight between the ages of 18 and 29. After the arrival of the subjects to the laboratory, blood pressure was taken and resting energy expenditure (REE) and respiratory quotient (RQ) were assessed for 20 minutes (Baseline) via indirect calorimetry. Half of the subjects were then given 75 mg of immediate-release PPA (administered orally via a gelatin capsule), while the other half received placebo. Immediately after drug administration, metabolic rate was measured for an additional 95 minutes (During Drug). After this assessment, blood pressure was again measured. Although significant increases in both systolic and diastolic blood pressure were observed after PPA administration, the drug had no effect on REE or RQ. These results, consistent with that previously reported in mildly overweight women, further establish that it is unlikely that drug-induced metabolic changes contribute to PPA-induced weight loss in humans.

Are weight concerns predictive of smoking cessation? A prospective analysis.

Participants in an 8-session, community based smoking cessation intervention rated whether they would stay quit if they experienced weight gain. The majority reported that they would not relapse to smoking, even after a 20-lb, (9.07-kg) weight gain. Those who were weight concerned were more likely to be female, to weight less and be normal or underweight, and to report chronic dieting. This group was also significantly less likely to be abstinent posttreatment, and at the 1-, 6- and 12-month follow-ups. Individuals presenting for formal smoking cessation interventions may be less weight concerned than the general population of smokers. However, weight-concerned smokers who do present for treatment are less likely to quit smoking. Implications for recruitment and intervention are discussed.

How much weight gain occurs following smoking cessation? A comparison of weight gain using both continuous and point prevalence abstinence.

Estimates of postcessation weight gain vary widely. This study determined the magnitude of weight gain in a cohort using both point prevalence and continuous abstinence criteria for cessation. Participants were 196 volunteers who participated in a smoking cessation program and who either continuously smoked (n = 118), were continuously abstinent (n = 51), or who were point prevalent abstinent (n = 27) (i.e., quit at the 1-year follow-up visit but not at others). Continuously abstinent participants gained over 13 lbs. (5.90 kg) at 1 year, significantly more than continuously smoking (M = 2.4 lb.) and point prevalent abstinent participants (M = 6.7 lbs., or 3.04 kg). Individual growth curve analysis confirmed that weight gain and the rate of weight gain (pounds per month) were greater among continuously smoking participants and that these effects were independent of gender, baseline weight, smoking and dieting history, age, and education. Results suggest that studies using point prevalence abstinence to estimate postcessation weight gain may be underestimating postcessation weight gain.

Effects of chronic phenylpropanolamine infusion and termination on body weight, food consumption and water consumption in rats.

The present study determined the effect of chronic PPA infusion and withdrawal on weight regulation. Male Sprague-Dawley rats received PPA (0, 90 or 180 mg/kg) via miniosmotic pumps for 2 weeks. Body weight and food and water consumption were measured daily before, during, and for 2 weeks after PPA infusion. Additionally, body weight was measured once 6 weeks after the last day of drug administration. PPA infusion produced dose-dependent reductions in body weight and food consumption throughout drug administration. During the first week of PPA termination, food consumption returned to control levels; however, body weights of drug-treated animals remained below those of controls throughout the 6-week post-drug period. PPA depressed water intake during the first week of drug administration, but tolerance to this effect developed by the second week of administration. These results suggest chronic PPA infusion produces persistent appetite suppression and weight loss and that discontinuation of PPA does not result in hyperphagia or rapid weight gain. These findings may have clinical significance for the many individuals who wish to lose weight but have difficulty reducing intake without pharmacologic assistance.

Effects of nicotine cycling on weight loss and regain in male rats.

Over successive periods of weight loss and regain caused by deprivation and refeeding, weight loss becomes slower during deprivation and weight is regained quicker during refeeding. One period of nicotine administration and termination results in changes in intake and weight gain comparable to that caused by one period of food deprivation and refeeding. However, no study has examined the effect of multiple periods of nicotine administration and cessation on weight loss and regain. The present study examined the effect of repeated cycles of nicotine administration and cessation on growth rate. Thirty-two male Sprague-Dawley rats underwent three nicotine administration cycles. Cycles consisted of 2 weeks of nicotine or saline followed by 2 weeks of no drug. Nicotine administration decreased growth and food consumption, and cessation resulted in a resumption of normal growth and intake. However, changes in food consumption and body weight were similar across cycles. Thus, although nicotine administration and cessation produced reliable changes in food consumption and body weight similar to those caused by diet cycling, there were no comparable cumulative effects of nicotine cycling on growth rate.

Effects of phenylpropanolamine on regulatory and nonregulatory ingestion in adult rats.

This experiment examined the effects of phenylpropanolamine (0.0, 5.0, 10.0, 20.0 mg/kg PPA) on regulatory (RG) and nonregulatory (NRG) eating and drinking in rats using a within-subjects design. Administration of PPA produced dose-dependent reductions in eating in animals deprived to 80-85% of baseline weight, and reduced drinking after 23.5-h of water deprivation. Nonregulatory eating, elicited by tail pinch in nondeprived animals, was similarly inhibited. Nonregulatory drinking was elicited in the schedule-induced polydipsia (SIP) paradigm. Water consumption, locomotion, licking, lick efficiency (licks/ml water), and entries into the food magazine were simultaneously measured. At the lowest dose, only locomotion was significantly reduced. At 10.0 mg/kg, lick efficiency and entries into the food magazine were also significantly reduced, while all measured behaviors, including licking and water consumption, were decreased by the highest dose of PPA. The reduction in lick efficiency suggested a PPA-induced motor impairment in the capacity for licking. Considered together, these results indicated that the observed decreases in regulatory and nonregulatory eating and drinking could be at least partially accounted for by the drug's effects on behaviors contributing to ingestion, as well as apparent motor impairments in ingestive behavior at higher doses.

Effects of phenylpropanolamine infusion and withdrawal on body weight and dietary composition in male and female rats.

Male and female rats with ad lib access to separate sources of carbohydrate, fat, and protein were implanted with minipumps providing one of three dosages (0.0, 40.0, or 80.0 mg/kg/day) of phenylpropanolamine (PPA) for 2 weeks. Body weight, macronutrient intake, and water consumption were measured daily before, during, and after PPA treatment. Phenylpropanolamine lowered body weight and caloric intake in males and females, and water consumption in females, but did not alter dietary composition in either sex. After PPA termination, caloric intake returned to control levels in both males and females. However, body weight returned to control levels in males only, while PPA-treated females continued to weigh less than controls. Phenylpropanolamine termination was associated with significant increases in water consumption and the percentage of total calories consumed from protein and reductions in the percentage of calories from carbohydrate in males. In contrast, water and macronutrient consumption was similar comparing PPA-treated females to controls after drug termination. These results suggest there are sex differences in the effects of PPA termination on water and macronutrient consumption that result in differential weight gain in males and females.

Use of phenylpropanolamine to reduce nicotine cessation induced weight gain in rats.

The present study was conducted to determine if phenylpropanolamine (PPA) administered during the first week of nicotine termination could reduce or eliminate the body weight rebound which accompanies nicotine cessation. Sprague-Dawley rats were administered nicotine for 2 weeks after which they received either PPA or saline for 1 week. Control animals received saline during both drug periods. Body weight, food consumption, and water consumption were measured daily before drug, during nicotine and PPA administration, and for 14 days after PPA administration. In contrast to animals receiving saline upon termination of nicotine, animals receiving PPA did not gain weight at an accelerated rate. Termination of PPA did not result in a body weight rebound. To the extent that these results generalize to humans, they suggest that PPA could be used to reduce or eliminate postcessation weight gain in smokers who stop smoking.

Gender differences in tobacco use.

Gender differences in overall tobacco use clearly exist. In general, men are more likely to use tobacco products than are women. However, this simple generalization, ignoring type of tobacco products, time, and culture, masks many more interesting gender differences in tobacco use. There are pronounced gender differences in tobacco use of specific tobacco products within some cultures but not others. Yet these differences have changed across time, including narrowing and widening of this gender gap, depending on culture and tobacco product. This article addresses these issues and presents possible psychosocial, biological, and psychobiological explanations for these phenomena. In addition, the implications of these differences and ways to learn more about these important differences are discussed.

Effects of nicotine on body weight, food consumption and body composition in male rats.

The present study examined the effects of nicotine administration and cessation on body weight, food consumption, and body composition in rats. Administration of nicotine was associated with attenuated body weight gains and cessation was associated with accelerated body weight gains. Changes in fat composition paralleled changes in body weight, whereas changes in body water and protein did not. These results suggest that nicotine administration decreases body weight through its effects on fat stores in the body. After cessation of nicotine, body fat rapidly approached levels of control animals.

Effects of chronic nicotine administration on insulin, glucose, epinephrine, and norepinephrine.

There is an inverse relationship between nicotine administration and body weight. Previous research indicates that this relationship results partially from effects of nicotine on energy intake. The present research includes two animal studies designed to investigate the effects of chronic nicotine administration on biochemical responses that affect energy utilization. The results indicate that chronic nicotine administration is accompanied by significant decreases in circulating insulin levels. Nicotine increases levels of catecholamines, but this effect is short-lived. The effects of nicotine on insulin are consistent with the conclusion that nicotine administration increases energy utilization.

Effects of nicotine on body weight in rats with access to "junk" foods.

The present experiment examined effects of nicotine on body weight of male and female rats when Oreo cookies, potato chips, laboratory chow, and water were available. Body weight and eating behavior were measured for 17-day periods before, during, and after nicotine or saline administration. There was an inverse relationship between nicotine and body weight. These effects were paralleled by changes in consumption of sweet foods. There were no effects of nicotine on salty or bland food consumption. Excessive gains in body weight after cessation of nicotine administration were greater for females than for males.

Sex differences in nicotine's effects on consummatory behavior and body weight in rats.

Nicotine administration and cessation have greater effects on body weight and eating behavior in female than in male rats. These generalizations are based on studies of body weight and eating behavior for 2-3 week periods before, during, and after nicotine administration. Therefore, the sex differences may reflect differences in sensitivity to nicotine or simply differences in the time course of nicotine's effects. The present research was designed to replicate these previous studies and to examine long-term effects of nicotine cessation on body weight. Nicotine or saline was administered SC to female and male Sprague-Dawley rats for 16 days. Body weight, food consumption, and water consumption were measured before, during, and after nicotine administration. In addition, body weight was measured for 4 months after cessation of nicotine. There was an inverse relationship between nicotine and body weight. Also, there was an inverse relationship between nicotine and general consummatory behavior for females but not for males. The body weight of females that had received nicotine were indistinguishable from controls up to 4 months after cessation of nicotine. The body weight of males that had received 12 mg nicotine per kg per day remained lower than controls.

Effects of nicotine on body weight and food consumption in female rats.

Women often report that they smoke cigarettes to avoid weight gains and that they relapse after abstaining from tobacco because of weight gains. Men also report these concerns but to a lesser extent. This gender difference may reflect sociological and cultural pressures about physical appearance, or it may reflect sex differences in the effects of nicotine. The present research was designed to examine the effects of nicotine administration and cessation of nicotine on body weight, food consumption, and water consumption. Alzet miniosmotic pumps were implanted SC to administer saline or three different concentrations of nicotine to female Sprague-Dawley rats for 17 days. This paradigm has been used in previous studies of nicotine and body weight in male rats. Animals were used as subjects to avoid cultural factors and cognitive concerns about body weight. Nicotine administration decreased normal body weight gains and cessation of nicotine was accompanied by significant increases in body weight compared to controls. In contrast to previous studies of male rats, the nicotine-related changes in body weight were accompanied by changes in bland food and water consumption. These findings indicate that females are more sensitive than males to the effects of nicotine on body weight and feeding during and after drug administration.