Effects Of Chronic Nicotine Administration Research Articles

Effects of chronic nicotine administration of 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.

Effect of chronic nicotine administration on monoamine and monoamine metabolite concentrations in rat brain.

The effects on rat brain tissue monoamine and monoamine metabolite concentrations of chronic nicotine administration at two doses (3 and 12 mg/kg/day) using constant infusion were studied. After 21 days of treatment, tissue concentrations of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and several metabolites in striatum, hypothalamus, and frontal cortex were determined by high performance liquid chromatography with electrochemical detection. Compared with a control group, nicotine treatment significantly decreased NE in frontal cortex but not in other regions. The concentration of 5HT also was decreased in frontal cortex but increased in the hypothalamus at the higher dose of nicotine. The 5HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was not significantly altered in any region. The 5HT index (5-HIAA/5-HT) was significantly decreased in the hypothalamus and increased in frontal cortex at the higher dose. Concentrations of DA and the metabolite homovanillic acid (HVA) were not significantly altered by nicotine. Nevertheless, significant decreases in the DA metabolite dihydroxyphenyl-acetic acid (DOPAC) were observed in both striatum and hypothalamus. Moreover, the DA index [(DOPAC + HVA)/DA] was significantly decreased in all three brain regions. In contrast to other studies using acute dose and in vitro perfusion paradigms that have reported increased CNS catecholamine release stimulated by nicotine, chronic administration appears to be associated with decreased catecholamine turnover in some brain regions.

Chronic nicotine and withdrawal effects on body weight and food and water consumption in female rats

Female rats were used to examine the effects of chronic nicotine administration and withdrawal on food and water consumption and body weight. Rats with chronic nicotine pellet implants consumed significantly less food and water than controls for the first five days and then gradually returned to control levels of consumption. The lowest level of body weight was reached on day 9 after which there was a slow return to control weights by day 21. When the nicotine pellets were removed from the short-term exposure group on day 14, they showed significant hyperphagia and hyperdipsia and a very rapid weight gain for the next several days, which clearly outpaced the recovery of weight in the long-term nicotine exposure group. These results show that in female rats changes in weight during chronic nicotine administration and withdrawal are accompanied by changes in rates of consumption. In addition, nicotine withdrawal can cause hyperphagia and hyperdipsia even though levels of consumption had previously returned to control levels and even though the route of nicotine administration was not oral.

Chronic nicotine administration increases binding of [3H]domperidone in rat nucleus accumbens.

An apparent inverse relationship between smoking and Parkinson's disease prompted an investigation of the effect of chronic nicotine administration on dopaminergic and serotonergic receptors in rat brain. Nicotine, 0.8 mg/kg, was injected once daily, five times per week, for 6 weeks. In nucleus accumbens the Kd for [3H]domperidone was increased 2-4-fold, and the Bmax was increased 1.5-2-fold. No changes were observed in the binding of [3H]domperidone in caudate-putamen or in that of [3H]ketanserin in frontal cortex. It is concluded that chronic nicotine administration may have a suppressant effect on central nervous system release of dopamine that in pre-parkinsonian persons causes an aversion to the effects of smoking.

The role of physical activity in nicotine's effects on body weight

The present study examined the effects of chronic nicotine administration and cessation of nicotine administration on body weight and 24-hour physical activity of rats. There was a significant, inverse, dose-effect relationship between nicotine administration and body weight. Cessation of nicotine was accompanied by increased rates of body weight gain compared to controls. The changes in body weight during nicotine administration could not be explained by changes in physical activity. However, decreases in physical activity after cessation of nicotine appeared to contribute to post-drug body weight increases. These findings have implications for weight control after cessation of cigarette smoking.

Effects of chronic nicotine administration on the response and adaptation to stress.

The effects of chronic nicotine administration (0.4 mg/kg for 40 days) and its withdrawal on the adrenocortical response to acute and repeated exposure to stress have been examined and related to changes in brain 5-hydroxyindole levels. No significant effects on the response to acute stress were observed. Repeated exposure to the stressful procedure resulted in complete adaptation of the adrenocortical response and the development of a significant (P less than 0.01) positive correlation between the plasma corticosterone and hippocampal 5-HT concentrations. In nicotine-treated rats, complete adaptation did not occur and the plasma corticosterone showed a significant (P less than 0.05) negative correlation with hippocampal 5-HT. Nicotine withdrawal was not associated with any reduction in plasma corticosterone, but did abolish its relationship with hippocampal 5-HT.

Effects of chronic nicotine administration on RBC velocity in mesenteric capillaries of the rat.

The purpose of this study was to determine the effects of chronic administration of nicotine on red blood cell (RBC) velocity in single capillaries of the mesentery. Ten male rats consumed an average of 2.38 mg nicotine/kg/day, an approximate '2 pack' equivalent, in their drinking water for a period of 15-20 weeks. At the end of this time RBC velocity was measured in single capillaries of the mesentery. The data were compared to RBC velocities measured in a group of matched control rats. Red cell velocities in the control and nicotine groups averaged 1.22+/-0.23 and 0.59+/-0.10 mm/sec SEM, respectively. These values were significantly different (p less than or equal to 0.01). It is concluded that chronic administration of nicotine to rats in levels equivalent to tobacco smoking reduces resting capillary blood flow in the mesenteric circulation as indicated by differences in erythrocyte velocity.

Effects of chronic nicotine administration on the denervated rat adrenal medulla.

1 The effects of chronic nicotine administration (1 or 10 mg/kg, s.c., twice daily) were studied in intact and denervated rat adrenal glands to determine the relative roles of central input and direct actions on catecholamines. 2 Catecholamine depletion was obtained in the intact glands from 1-7 days of treatment with 10 mg/kg, with recovery by 14 days of treatment; catecholamines were not decreased in denervated adrenal glands. 3 Catecholamine depletion was accompanied by a decline in functional storage vesicles (determined by [3H]-adrenaline uptake per gland) in the intact side, while no change was seen in the denervated side; the proportion of newly synthesized vesicles increased markedly during 1-7 days of treatment with 10 mg/kg in the intact side, while a much smaller increase of shorter duration was seen in the denervated adrenal gland. 4 Chronic nicotine administration at either dose level induced tyrosine hydroxylase in both intact and denervated glands, but the increase occurred more slowly in the denervated glands. 5 Dopamine beta-hydroxylase levels increased similarly in both sides during treatment with nicotine (10 mg/kg). 6 These studies suggest that although long-term adrenal denervation eliminates the catecholamine depletion caused by chronic administration of nicotine, the mechanisms for induction of catecholamine synthesizing enzymes are still capable of responding to the drug.

Effects of chronic nicotine administration and age on various neurotransmitters and associated enzymes in male Fischer-344 rats

The acute, subacute and chronic effects of nicotine have been studied in male Fischer-344 rats. Two-month-old animals were injected sc with either 1.0 ml of 0.85% w v NaCl/kg/day, or 1000 μg nicotine base/ml/kg/day for 4 days or for 2 or 22 months; injectables were formulated in 6% gelatin. Nicotine pretreatment did not significantly alter 5-hydroxytryptamine (5-HT) or norepinephrine (NE) concentrations in a variety of tissues, nor whole brain choline (Cho), acetylcholine (ACh) and acetylcholinesterase activity. γ-Aminobutyric acid concentrations in 8 brain areas were all higher after chronic nicotine administration, but histamine (HM) concentrations were variably affected in a variety of tissues. The uptake of 5-HT into the heart and gastrointestinal mucosa, and of NE into the heart and aorta, was not affected by nicotine treatment. However, uptake of NE into synaptosomes prepared from an homogenate of whole brain was depressed. Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion was significantly higher in nicotine-treated rats compared to control animals both during ad libitum feeding and during food deprivation. In addition, urinary 5-HIAA excretion was significantly higher in nicotine-treated rats with food deprivation compared to ad libitum feeding. Histidine decarboxylase (HD) and dopa decarboxylase (DD) activities in a variety of tissues were variably affected by nicotine; however, both enzymes showed diminished activity in the gastric mucosa following the alkaloid. Cardiac, aortic and hepatic catechol- O-methyltransferase (COMT) activity was not altered by nicotine administration. Hepatic, aortic and cerebral monoamine oxidase (MAO) activity was unchanged, but an increase in myocardial activity, and a decrease in hepatic activity were observed depending upon the substrate. Several changes were observed between young (4-month-old) and old (24-month-old) rats. Bone marrow (femur) 5-HT and HM concentrations decreased with age, whereas 5-HT levels in the gastrointestinal area, and HM concentrations in general, increased with age. Uptake of NE and 5-HT into the heart was reduced with age, whereas HD and DD activity showed no consistent change in the tissues examined. COMT activity significantly increased in the liver and aorta, but not in the heart, with age. Conversely, MAO activity increased in the myocardium but not in the liver, brain or aorta, with age.

Effects of chronic nicotine administration and age in male Fischer-344 rats

The chronic effects of nicotine were studied in male Fischer-344 rats over periods of 2 or 22 months. Nicotine (1000 μg base/ml/kg/day) was given sc in 6% gelatin, whereas control rats received 0.85 g/100 ml w/v NaCl in 6% gelatin. Nicotine-treated rats achieved and maintained a significantly lower ( p < 0.01) weight gain than control animals, and the weight of several tissues in both control and nicotine-treated groups showed a change with age. There was no significant change in hemoglobin, or hematocrit, or mean corpuscular volume, hemoglobin, and hemoglobin concentration, or in red and white blood cell counts between control and nicotine-treated rats. Similarly, the differential white cell count did not differ between the 2 groups; however, an increasing percentage of neutrophil polymorphonuclear leucocytes and a decreasing percentage of lymphocytes was shown for both groups with age. Platelet number and morphology were not altered. Several neoplasms developed in the animals injected for 22 months. Two tumors, an adenocarcinoma of the lung and chromophobe adenoma developed in the 6 old control rats (33%), and 9 tumors (3 instances of pheochromocytoma, 4 cases of epidermoid carcinoma of the skin, 1 rat with leukemia and 1 animal with fibrosarcoma) developed in 8 of the old treated rats (29%). The incidence of Leydig cell hyperplasia differed significantly with lesions developing in 66% of the old control rats compared to 89% of the old treated rats ( p < 0.05). It is possible that the physiologic age of the nicotine-treated rats was significantly greater than the controls, and thus the animals were at greater risk for the development of this lesion. Nicotine administration had no effect on the Ca 2+-dependent myosin ATPase activity or on the lactic dehydrogenase activity and isozyme pattern from predominantly fast (gastrocnemius), slow (soleus) or cardiac muscles. Mg 2+-dependent ATPase activity from soleus muscle myofibrils was considerably depressed after 22 months of nicotine treatment, whereas activity from cardiac and gastrocnemius muscles was unchanged.

Lack of effect of chronic nicotine administration on fatty acid distribution in the liver, testis, and adipose tissue of male Fischer-344 rats

A comparison is made of the percentage compositions of major fatty acids in liver and testis phospholipids, liver and abdominal adipose tissue triglycerides, and liver sterol esters in male Fischer-344 rats administered a physiological saline control or a "smoking" dose of nicotine (1000 micro g base/kg/day, subcutaneously) for 2 or 22 months. Results indicate that there is no major trend, or significant difference, between nicotine- or saline-treated rats with respect to major fatty acid distribution. Some differences in fatty acid distribution in the various lipid fractions were found between young and old rats.