Repeat to nicotine tolerance in rats cooled reaction and the impact of activities and body weight
Authors: Yong-Lu Huang Tao Meng, Shen Zi-Ling HAN Qin
【Abstract】 Objective To observe the repetition to the nicotine in rats
as well as temperature tolerance response activity and body weight effects. Methods Using wireless telemetry technology to monitor body temperature and activity in rats were observed for 5 days repeated injection of small doses of nicotine (0.5 mg / kg) on the SD rat body
temperature, activity and body weight effects. Results ? for the first
time after the rats were given injections of nicotine can lead lasted about 1.5 h of cooling response; but the third injection of nicotine, the body temperature of male and female rats were similar to the control group. ? Repeat to nicotine can significantly reduce the body weight. ?
each injection of nicotine and saline animals, the activities can cause a brief increase in response; from the second to fifth after the second
injection of nicotine the activities of female rats was higher than that in male rats. Conclusion repeated injections of nicotine can lead to male and female rats exhibited a temperature tolerance response, but a continuous injection of nicotine, the activities of female rats
significantly higher than male rats. In addition, repeated to nicotine can reduce the male and female rats of the growth rate.
Key words nicotine; low temperature; the body temperature too high; gender differences in
【Abstract】 Objective To observe the repeated nicotine exposure lead to tolerance of hypothermic effect and the effect on motor activity and body weigh in rats. Methods The effects of daily injections of nicotine at small dosage (0.5 mg / kg) once a day for 5 days on core temperature and
motor activity in male and female Sprague Dawley rats were monitored by
radio telemetry. Results ? The first injection of nicotine in rats led to a hypothermic response for approximately 1.5 hours. But after the third
injection of nicotine, changes of core temperature in male and female rats were similar to controls. ? Repeated treatment with nicotine
significantly reduced body weight. ? Motor activity also increased
transiently with each injection of saline and nicotine, but the motor
activity response of females was significantly greater than the males for the second through fifth injections of nicotine. Conclusion The results of this study show that repeated injection of nicotine can lead to tolerance of hypothermic response, but motor activity response of females was significantly greater than the male rats after sequential nicotine injections. In addition, repeated nicotine treatment attenuated the growth of male and female rats.
【Key words】 Nicotine; hypothermia; tolerance; body weight
Thermoregulation center in the hypothalamus is rich in nicotinic acetylcholine receptor (N R) and muscarinic receptor (M receptor), both of which are involved in human and mammalian thermoregulation process. M receptor agonist tremor hormone and N oxidation of nicotine receptor agonists can be aroused through the blood-brain barrier into the central
cooling rodents apparent reaction [1 2]. Although experiments have
shown that nicotine is not only involved in the process of cooling, but
cooling can occur repeatedly to nicotine tolerance response or affect the sensitivity of acetylcholine receptors [2 4], but no small dose of
nicotine caused by temperature changes and resistance to sexual response time curve characteristics and the activity and body weight change and gender differences were reported. By considering the wireless telemetry technology can not only cause a continuous and accurate record of repeated administration of the changes in body temperature and activity, but it can
also avoid manual repeated measurements colonic temperature changes caused by animal activity, and stress-induced hyperthermia on experimental
outcomes. Therefore, this experiment with wireless remote temperature measurement technology, continuous observation of rats were given repeated injections of small doses of nicotine in it have a cool tolerance response, but also demonstrated that repeated injections of nicotine on the impact of animal activity and body weight and gender differences.
1 Materials and methods
1.1 Experimental animals and reagents
Experiments with adult male and female SD rats (Experimental Animal Research Institute, Sichuan Academy of Medical Sciences provided), weighing 200 ~ 250g. Nicotine hydrogen tartrate (Nicotine hydrogen
tartrate) for the Sigma's products, with normal saline preparation of the required experimental concentrations of different doses.
1.2 Experimental groups and procedures
Experiment is divided into two parts to complete. Experiment 1:
Different doses of nicotine on male and female rats with body temperature and activities. Male and female rats were each divided into 4 groups (n = 7), namely, normal saline group and 0.25 mg / kg, 0.5 mg / kg and 0.75 mg / kg nicotine group, injection volume were 1ml/kg. 1 day before the experiment at 4 pm, the rats were placed in clean cage, and then placed in SH 800GS artificial climate chamber (Chongqing Experimental Instrument Factory eternal life product) within the adaptive overnight, animals in a
free activity, feeding and waterState. Artificial climate inside temperature setting is 25 ?, humidity 70% ~ 80%, light and dark time,
each for 12 h, turn on the lights at 6 am, 6 pm lights. Experiment began at 6 am the day of a continuous record of temperature and activity in rats, at 11 am, respectively, to animals, subcutaneous injection of different doses of nicotine or saline, the continuous recorded at 3 pm end of the experiment.
Experiment 2: Low-dose repeated subcutaneous injection of
nicotine on body temperature, activity and body weight effects. Male and female rats were each divided into 2 groups (n = 7), namely, saline and nicotine groups. 2 days before the experiment at 4 pm, the rats were placed in the artificial climate chamber, artificial climate chamber parameter setting with the experimental one. 1 day before the experiment began at 6 am and activities of a continuous record of temperature, experiments were injected subcutaneously at 11 am the day of nicotine 0.5
mg / kg (0.5mg/ml normal saline) or saline 1 ml / kg, daily administration of 1 times continuous injection of 5 days.
1.3 Animal Surgery
With 4% intraperitoneal injection of sodium pentobarbital anesthesia (40 mg / kg) animals, in accordance with conventional surgical
incision abdominal skin and muscles, implanted radio telemetry temperature probe (Data Sciences international, model TA10TA F40), the suture
abdominal muscles and skin, and intramuscular injection of penicillin to
prevent infection. After the animals were kept in individual plastic cages in rats more than 10 days to resume the experiment. Laboratory temperature of 23 ? ~ 25 ? or so, light and dark time, each for 12 h, 6 am to 6 pm for the day-light (lights), 6 pm to 6 am the next day for the dark light
1.4 Temperature measurements and to determine indicators of changes in body temperature
Temperature measurement system with wireless remote control (the United States DSI's products) measurements of body temperature in rats,
the abdominal cavity with built-in wireless temperature telemetry probe
into the clean cage in the rat, and then put the receiver on-board remote
thermometer, large rat intra-abdominal wireless telemetry probe interval
of 5 min acquisition time for each body core temperature signals received
by the receiver board, enter the computer storage and data processing.
Temperature response indicators with an average thermal response curve and the thermal response of the most significant difference between
the baseline temperature (? T), said.
Weighing 1.5 weight
Daily at 11 am with electronic weighing scales body weight, repeatability error of <0.1 g.
1.6 Statistical Analysis
Experiment 1 data is the interval of 5 min for each experimental group, calculated from data as mean ? standard deviation (? s), said the
experiment two of the experimental data is recorded in 5 min intervals of the experimental data were calculated as the number of hourly ? standard
deviation of that, and then use paired t test or group comparison t test was used for statistical analysis.
2 Experimental results
2.1 of different doses of nicotine on male and female rats with body temperature and activities
From Table 1 shows that the rats were injected with normal saline control group suffered from body temperature after the reaction, this phenomenon is due to injecting drugs and mobile animals, caused by increased activity due to stress-induced hyperthermia response.
Subcutaneous injection of 0.25 mg / kg nicotine could significantly prevent the stress-induced hyperthermia in rats sexes reaction; injection of 0.5 mg / kg nicotine 20 min after the male and female rats suffered from mild hypothermia response, the administration of post-50 min body
temperature returned to control levels; to the male injection 0.75 mg / kg nicotine 20min, the low-temperature reaction of the most significant
hypothermia compared with pre-administration up to 0.8 ?, at 90min after
administration body temperature returned to control levels; and female rats were injected 0.75 mg / kg of nicotine caused after the low-
temperature reaction and 0.5 mg / kg were similar. Table 1 subcutaneous injection of different doses of nicotine on rat body temperature affect the reposted elsewhere in the paper for free download http://
2.2 The repeated injection of small doses of nicotine on rat body
temperature and activities with the gender differences
The first subcutaneous injection of nicotine (0.5 mg / kg), the animal body temperature was significantly lower than saline group and lasted about 2 h, but administration of pre-cooling the body temperature
was no reaction (Figure 1), appears inconsistent with the experimental results of a phenomenon mainly the different statistical methods and data related. In Experiment 2, a continuous collecting 144 h up to 6 days the amount of data points for each drawing will only take 1 h, on average, this masks the low-temperature reaction of nicotine caused by short-term
process of change; one due to the experimental observation of the duration of the more a short interval of each drawing point is only 5min, they are
able to accurately reflect the changes in body temperature during
Every time the rats were injected with normal saline can cause stress-induced body temperature response, but repeated injection of saline for 5 days after stress in rats appeared slightly lower body temperature response to the phenomenon. Nicotine group of animals in the third after the second injection of nicotine similar to temperature changes and saline group, fourth and fifth after the second injection of nicotine body
temperature was significantly higher than saline group (Figure 1). In addition, it is interesting that the male rats in the third and fourth after the second injection of nicotine to 6 pm the animals into the dark photoperiod significantly increased body temperature, that is a normal
cyclical rise in body temperature relative to body temperature were significantly higher than About sustained 5 h ~ 6 h (Figure 1). Figure 2 Further analysis shows that female rats of the third and fourth after the second injection of nicotine body temperature response is similar.
In addition, the impact of nicotine on rat activity has a clear gender differences. Continuous injection of nicotine can cause an increase in female rats the activities of the phenomenon, that is, from the second
to fifth after the second injection of nicotine, the activities of female rats compared with saline group was significantly increased, but the activities of male rats compared with saline group no significant difference (Figure 3).
2.3 The repeated injection of small doses of nicotine on body weight of
Repeated subcutaneous injection of small dose of nicotine (0.5 mg / kg) may slow down the growth rate of rats. The fifth male rats after the injection of nicotine and saline, body weight were -1.5 ? 2.7g and 5.1 ?
2.9g; female rats after the fifth dose, body weight were 0.71 ? 1.0g and
5.0 ? 1.0g .
In this study, rats were given subcutaneous injection of different doses of nicotine administered after the temperature change and earlier, 0.25 mg / kg of nicotine significantly inhibited the male and female rats stress-induced hyperthermia response, 0.5 mg / kg can cause Gender in rat body temperature lower than the average before the administration of
0.48 ?, 0.75 mg / kg caused more pronounced effect of low temperature (Table 1), indicating that a small dose of nicotine can cause not only the low-temperature reaction, and a clear dose-effect relationship. Caused by
subcutaneous injection of nicotine into the body temperature of this low-
temperature reaction and the central regulation of nicotine can promote the thermal reaction of the [2,6,7].