5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats

Numerous studies support a role for the endogenous 5-hydroxytryptamine (5-HT) system in the hypothermic effect of capsaicin. None of those studies, however, selectively delineate a role for 5-HT reuptake or 5-HT receptors in this regard. In the present investigation, we determined if the blockade of 5-HT reuptake or the activation of 5-HT_1A or 5-HT₂ receptors modulates capsaicin-evoked hypothermia. The administration of capsaicin (0.2–1 mg/kg, i.m.) produced dose-related hypothermia. Fluoxetine (10 mg/kg, i.p.), a selective serotonin reuptake inhibitor (SSRI), did not affect body temperature. For combined administration, pretreatment with fluoxetine (10 mg/kg, i.p.) significantly attenuated the hypothermia caused by capsaicin (0.5 and 1 mg/kg, i.m.). For the 5-HT receptor experiments, we pretreated rats with either WAY 100635, a 5-HT_1A receptor antagonist, or mianserin, a 5-HT₂ receptor antagonist, and then administered a fixed, hypothermic dose of capsaicin (1 mg/kg, i.m.). WAY 100635 (1 mg/kg, s.c.) administration did not affect capsaicin-evoked hypothermia. This indicates that 5-HT_1A receptor activation does not play a major role in the hypothermic effect of capsaicin. In contrast, pretreatment with mianserin (10 mg/kg, i.p.) enhanced the hypothermic effect of capsaicin (1 mg/kg, i.m.). The present data reveal that capsaicin-evoked hypothermia in rats is attenuated by the blockade of 5-HT reuptake and enhanced by the antagonism of 5-HT₂ receptors.     

Serotoninergic mechanisms of beta-endorphin-induced hypothermia in rats

The effects of intraventricular administration of beta-endorphin on thermoregulatory responses of unanesthetized rats to different ambient temperatures (T _a ) of 8, 22 and 30°C were assessed. Administration of beta-endorphin produced a fall in rectal temperature at bothT _a 8 and 22°C. The hypothermia in response to beta-endorphin was brought about by both cutaneous vasodilation (as indicated by an increase in both the tail and the foot skin temperatures) and decreases in metabolic heat production. However, atT _a 30°C, administration of beta-endorphin produced no change in rectal temperature or other thermoregulatory responses. Furthermore, the hypothermic effect induced by beta-endorphin was greatly attenuated by either the depletion of brain serotonin levels (with 5,6-dihydroxytryptamine andp-chlorophenylanine) or the blockade of opiate receptors (with naloxone). The data indicate that beta-endorphin leads to hypothermia in rats by increasing sensible heat loss and decreasing metabolic heat production, probably via the release of endogenous serotonin within brain.     

WAY100635 blocks the hypophagia induced by 8-OH-DPAT in the hypothalamic nuclei

This study examined the influence of pretreatment with N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide maleate (WAY100635, full 5-HT1A receptor antagonist, 37 nmol) on feeding effects evoked by local injections of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 5-HT_1A and 5-HT₇ receptor agonist, 6 nmol) into the LH and into the ARC of female rats adapted to a wet mash diet (enriched with 10% sucrose), during diestrus or estrus. The results showed that the LH-pretreatment with WAY100635 suppressed the hypophagic effects evoked by 8-OH-DPAT during estrus as well as diestrus. The ARC pretreatment with WAY100635 blockaded the hypophagia evoked by 8-OH-DPAT in estrus rats. The previous treatment with WAY100635 in the ARC also suppressed the feeding duration decrease evoked by 8-OH-DPAT in estrus. The latency to start feeding, the drinking behavior and the durations of other non-ingestive behaviors were not affected by the different treatments, hypothalamic regions (LH or ARC), and/or estrous cycle stages (diestrus and estrus), except for the locomotion duration increase after 8-OH-DAPT in LH-pretreated rats in diestrus. The present findings confirm our previous suggestion that ARC- and the LH-5-HT_1A receptors participate in the serotonergic control of feeding and that these feeding-related serotonergic circuits in LH are affected by ovarian hormones, since the treatment with WAY100635 evoked a hypophagia response during the diestrus phases.     

Selective blockade of peripheral delta opioid agonist induced antinociception by intrathecal administration of delta receptor antisense oligodeoxynucleotide

Previous studies have shown that intrathecal (i.t.) administration of antisense, but not mismatch, oligodeoxynucleotides (ODNs) to the cloned delta opioid receptor (DOR) can inhibit the antinociceptive actions of i.t. delta (δ), but not mu (μ) or kappa (κ), opioid agonists. As a major portion of spinal opioid receptors are localized on the central terminals of the small afferent fibers, we hypothesized that the effects of antisense ODNs given i.t. might be the result of actions at the level of the cell body in the dorsal root ganglion (DRG). This possibility was investigated by assessing the antinociceptive actions of an i.t. or intrapaw (ipaw) administered μ (morphine), δ ([ -Ala², Glu⁴]deltorphin) or κ (CI977) opioid agonist in rats treated with i.t. saline or antisense or mismatch ODNs to the DOR (12.5 μg, twice-daily for 3 days). The opioid agonists produced significant antinociception in the 5% formalin-flinch test following either i.t. or ipaw administration. DOR antisense ODN treatment blocked the antinociceptive actions of both i.t. or ipaw [ -Ala², Glu⁴]deltorphin without affecting the antinociceptive actions of i.t. or ipaw morphine or CI977. Radioligand binding studies with [³H]naltrindole (NTI), a δ selective antagonist, indicated an approximate 50% decrease in δ opioid receptors in the lumbar spinal cord following i.t. DOR antisense, but not mismatch, ODN treatment. DOR antisense or mismatch ODN treatment did not affect ν or κ radioligand binding in lumbar spinal cord. These data suggest the possibility that peripheral proteins can be targeted with i.t. antisense ODNs providing significant opportunities for the exploration of the physiological and pathological significance of these substances.     

Ondansetron and fluoxetine reduce sleep apnea in mice lacking monoamine oxidase A

Prospective clinical trials addressing the role of serotonin (5-HT) in sleep apnea have indicated that the 5-HT uptake inhibitor fluoxetine is beneficial to some patients with obstructive apnea, whereas the 5-HT₃ receptor antagonist ondansetron seems of little value despite its efficacy in rat and dog models of sleep apnea (central and obstructive). Here, we examined the effect of these drugs in transgenic mice lacking monoamine oxidase A (Tg8), which exhibit 3-fold higher rates of central sleep apnea than their wild-type counterparts (C3H), linked to their enhanced 5-HT levels. Acute ondansetron (2 mg kg⁻¹, intraperitoneal), acute fluoxetine (16 mg kg⁻¹) and 13-day chronic fluoxetine (1 or 16 mg kg⁻¹) decreased by 80% the total (spontaneous and post-sigh) apnea index in Tg8 mice during non-rapid eye movement sleep, with no statistically significant effect on apnea in C3H mice. Our study shows that both drugs reduce the frequency of apneic episodes attributable to increased monoamine levels in this model of MAOA deficiency, and suggests that both may be effective in some patients with central sleep apneas.     

Involvement of nitrergic and opioidergic systems in the hypothermia induced by cholestasis in rats

Background and aim: Cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli and decreased febrile response to lipopolysaccharide. The present study was undertaken to determine if obstructive cholestasis was associated with abnormal thermoregulation under thermoneutral conditions. Methods: Male Sprague–Dawley rats weighing 200–250 g were randomly divided into 21 groups. Three sets of seven groups were unoperated control, sham-operated and bile duct-ligated rats. The groups of unoperated control, sham-operated and bile duct-ligated rats were treated with daily administration of isotonic saline solution, N(ω)-nitro-l-arginine methyl ester (l-NAME) (3, 10, or 20 mg/kg), naltrexone (10 or 20 mg/kg) or aminoguanidine (150 mg/kg). Body temperatures were measured before and 1, 3, 5 and 7 days after the surgery. Results: Bile duct-ligated rats had lower body temperature than sham-operated animals at 3 (P < 0.001) and 5 (P < 0.01) days after surgery. l-NAME, a non-selective inhibitor of nitric oxide synthase (NOS) (10, 20 mg/kg, i.p.) or aminoguanidine, a selective iNOS inhibitor (150 mg/kg, i.p.), completely reversed this hypothermia (P > 0.05). Naltrexone, a non-selective opioid antagonist (20 mg/kg, i.p.), also completely corrected this hypothermia (P > 0.05). There was a drop in temperature in the first day after the surgery in sham and BDL groups compared to unoperated controls, which was significant in some groups demonstrating the effect of surgery and anesthetic drugs on the body temperature. Conclusions: Cholestatic rats show impaired thermoregulation suggesting the involvement of nitrergic and opioidergic systems.     

内源性精氨酸加压素在索曼引起的大鼠体温降低中的作用

目的:探讨内源性精氨酸加压素是否参与索曼引起的降温过程。方法:用数字体温计测量大鼠的体温,每次间隔60 min,观察了腹腔注射AVP V₁受体阻断剂(30 μg/kg)对皮下注射索曼(60 μg/kg)引起大鼠降温效应的影响,以及给索曼后2 h血浆中AVP含量的变化。结果:给索曼后可引起明显的体温降低,在给药后7 h体温恢复到基线水平。AVP V₁受体阻断剂能明显阻断索曼的降温效应。在给索曼后2 h血浆中AVP浓度明显提高。结论:实验结果证明内源性AVP参与索曼引起的降温过程。     

Protective effects of melatonin on long-term administration of fluoxetine in rats

The degree and consequence of tissue injury are highly regarded during long-term exposure to selective antidepressant fluoxetine. Melatonin has been shown to palliate different lesions by scavenging free radicals, but its role in the reduction of the fluoxetine-induced injuries has been little known.Thirty-six mature male Wistar rats were randomly assigned into control and experimental groups. The experimental rats were included as following; 24 mg/kg/bw fluoxetine for 4 weeks; 1 mg/kg/bw melatonin for 4 weeks; fluoxetine + 1-week melatonin, fluoxetine + 2-week melatonin and fluoxetine + 4-week melatonin. In the current experiment, we investigated weight gain, hematological and biochemical parameters, pathological injuries and oxidative status.We noted the positive effect of melatonin in weight loss of fluoxetine-treated rats (p < 0.05). The significant reduction of superoxide dismutase, glutathione peroxidase, catalase activities in blood, liver, and kidneys and changes in serum total antioxidant capacity caused by fluoxetine were reversed by melatonin (p < 0.05). Melatonin reduced the increased lipid peroxidation and transaminase activity in rats received fluoxetine (p < 0.05). We also showed the potency of fluoxetine in inducing leukopenia, thrombocytopenia and hypochromic and macrocytic anemia which was blunted by melatonin. Both RBCs and platelets indices were also corrected. Rats received melatonin in combination with fluoxetine showed a reduction in the severity of degeneration and inflammatory changes in different tissues, brain, heart, liver, lungs, testes and kidneys as compared to the fluoxetine group.Therefore, melatonin fundamentally reversed the side effects of fluoxetine in the rat model which is comparable to human medicine.     

Effect of mild hypothermia on angiogenesis in rats with focal cerebral ischemia

In the present study, we investigated the effect of mild hypothermia on infarct volume, angiogenesis and brain-derived neurotrophic factor (BDNF) level after stroke. After permanent middle cerebral artery occlusion, mild hypothermia was induced immediately and maintained for 24h. 2,3,5-Triphenyltetrazolium chloride (TTC) staining, laser scanning confocal microscopy (LSCM) and ELISA were performed to assay infarct volume, angiogenesis and BDNF level in the ischemic boundary zone (IBZ), respectively. Compared with normothermic group, mild hypothermia reduced total infarct volume and increased endogenous BDNF level. And the microvessel diameter, the number of vascular branch points and the vessel surface area were significantly increased in the mild hypothermia group. These findings suggest that mild hypothermia enhances angiogenesis in ischemic brain, which might be enhanced in part via BDNF.     

体温过低对大鼠脑干听觉诱发电位和中潜伏期反应的影响

目的：探讨体温过低对大鼠脑干听觉诱发电位（BAEP）和中潜伏期反应（MLR）的影响。方法：计算机平均叠加技术颅表记录大鼠BAEP和MLR，体表物理降温法逐步降低大鼠体温，传感探头式数字体温计监测大鼠直肠温度，体温每降低1 ℃测试1次BAEP和MLR，观察波峰潜伏期（PL）和波幅的变化及各波消失的临界体温。结果：随体温逐渐降低（36 ℃-22 ℃），BAEP和MLR各波PL逐步延长；BAEP Ⅰ、Ⅱ、Ⅳ 3主波和MLR N1、P3 2主波的波幅在体温过低至26 ℃以下时方先后出现显著降低；BAEP和MLR各波在体温19 ℃-21 ℃全部消失，且两者同步消失。结论：体温过低对大鼠BAEP和MLR均有显著影响。     

Cerebral metabolic effects of fluoxetine,fluvoxamine, paroxetine and sertraline in the conscious rat

The selective serotonin reuptake inhibitors (SSRI) exert a wide range of neurochemical and therapeutic activities. To investigate the neural effectors of SSRIs, we measured the regional cerebral metabolic rates for glucose (rCMRglc) in 56 brain regions of Fischer-344 rats 30 min after intraperitoneal injection of 0.4, 4 or 40 mg/kg of fluoxetine or fluvoxamine or after 4 mg/kg of paroxetine or sertraline. Both shared and drug-specific effects were detected. While all four SSRIs similarly reduced rCMRglc in a network of subcortical brain regions including the amygdala, locus coeruleus, basal ganglia and hypothalamic paraventricular nuclei, fluvoxamine, paroxetine and sertraline reduced rCMRglc also in the hippocampus and sertraline in the lateral habenula. The topography and the relation to dose of rCMRglc reductions by SSRIs differ from those of other classes of antidepressants, thus suggesting that SSRIs may specifically modulate brain areas involved in the physiological responses to stress.     

Postnatal fluoxetine treatment affects the development of serotonergic neurons in rats

The goal of the present study was to investigate morphological changes in the serotonergic neurons/terminals in the dorsal (DR) and median (MnR) raphe nuclei and on the hippocampal dentate gyrus (DG) in neonatal rats treated from the 1st to the 21st postnatal day with fluoxetine (10 mg/kg sc, daily) or drug vehicle (0.9% saline 1 ml/kg). The results show that postnatal chronic treatment with fluoxetine promoted: (1) a smaller body weight increase during the pre-weaning period; (2) smaller number of 5-HT neurons in the DR; (3) smaller 5-HT neuronal cell bodies (area, perimeter and diameter) in the DR and the MnR and (4) diminished serotonergic terminals in the DG. These data suggest that the development of the serotonergic system was impaired and that early exposure to fluoxetine damaged the morphology of 5-HT neurons in young adult rats. While these findings are consistent with other work, more studies are needed to better clarify the effects of postnatal chronic treatment with fluoxetine on the serotonergic system and, consequently, on the functions modulated by serotonin.     

Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats

OBJECTIVES

: To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion.

METHODS:

Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10-g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats'' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared.

RESULTS:

Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six-week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups.

CONCLUSION:

Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats.     

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the present data show that the initial block of 5-HT reuptake is revealed by the selective increase in 5-HT levels (extracellular content) measured in PRP (not in insulated platelets, IPs) the 1st day of fluoxetine treatment. The initial action of this SSRI upon the 5-HT transporter in brain has also been confirmed by in vivo voltammetric data showing selective increase in the serotonergic signal following local injection of fluoxetine into the brain region studied. Successively, the major effect monitored is a decrease in 5-HT levels, which is more evident in IPs than in PRP. However, it is known that following 2 weeks treatment with an SSRI, 5-HT autoreceptors are desensitized and the serotonin synthesis is restored, together with the intracellular 5-HT levels. The present data showing that the levels of 5-HT in IPs tend to return to control values 12 days after the beginning of chronic fluoxetine treatment suggest that 5-HT levels in IPs (intracellular environment) mirror the influence of SSRI treatment upon the central 5-HT system. On the other hand, at day 12 of the chronic fluoxetine treatment, 5-HT content remains low in PRP. Similarly, low levels of 5-HT have been monitored in brain homogenate of rats chronically treated with fluoxetine. This would support the similarity between PRP preparation and brain homogenate as in both cases cells are disrupted by sample preparation. In conclusion this work supports the literature in proposing platelets as a peripheral model of central functions. In particular, the present data support the idea that peripheral 5-HT platelet levels can reflect the state of the central 5-HT system in conditions of depression. Furthermore, the main outcome of this study is that PRP may mirror central extracellular 5-HT levels, whilst IPs mirror neuronal 5-HT changes.     

Involvement of median raphe nucleus 5-HT1A receptors in the regulation of generalized anxiety-related defensive behaviours in rats

Changes in 5-HT_1A receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g. inhibitory avoidance) but not with panic (e.g. escape). The objective of this study was to further explore the involvement of MRN 5-HT_1A receptors in the regulation of generalized anxiety-related behaviours. Results of experiment 1 showed that intra-MRN injection of the 5-HT_1A/7 receptor agonist 8-OH-DPAT (0.6 nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance, without interfering with the performance of escape in the elevated T-maze test of anxiety. Pre-treatment with the 5-HT_1A receptor antagonist WAY-100635 (0.18 nmol) fully blocked this anxiolytic-like effect. As revealed by experiment 2, intra-MRN injection of 8-OH-DPAT (0.6, 3 or 15 nmol) also caused anxiolytic effect in rats submitted to the light–dark transition test, another animal model that has been associated with generalized anxiety. In the same test, intra-MRN injection of WAY-100635 (0.18, 0.37 or 0.74 nmol) caused the opposite effect. Overall, the current findings support the view that MRN 5-HT neurons, through the regulation of 5-HT_1A somatodendritic autoreceptors, are implicated in the regulation of generalized anxiety-associated behaviours.     

The effects of mirtazapine and fluoxetine on hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats

The use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") as a recreational drug has spread worldwide. Fatal hyperthermia is a likely side effect of using MDMA in combination with monoamine oxidase inhibitors. However, most antidepressants do not pose a high risk of developing hyperthermia when used in conjunction with MDMA. Mirtazapine is a novel antidepressant and a potent 5-HT(2A) receptor antagonist. It remains to be elucidated whether mirtazapine is unlikely to have life-threatening implications in combination with MDMA. In the present study, we evaluated whether mirtazapine and fluoxetine influence MDMA-induced hyperthermia in rats. The rectal temperature of the rats increased to above 41°C following an injection of MDMA (10mg/kg). Pre- and post-treatment administration of mirtazapine (5mg/kg) significantly attenuated MDMA-induced hyperthermia. Administration of WAY100635 (1mg/kg), a 5-HT(1A) receptor antagonist, did not influence the ability of mirtazapine to decrease hyperthermia induced by MDMA. Although pretreatment administration of fluoxetine (10mg/kg) significantly attenuated MDMA-induced hyperthermia, post-treatment administration of the same drug had no effect. The differences in body temperature between the groups post-treated mirtazapine and the groups post-treated fluoxetine may be due to differing mechanisms of action of the two antidepressants. The present study indicates that mirtazapine is unlikely to induce fatal hyperthermia when used with MDMA, and it may be rather effective against MDMA-induced hyperthermia. Considering our previous study demonstrating that potent 5-HT(2A) antagonists completely inhibit MDMA-induced hyperthermia, the findings of the present study suggest that mirtazapine inhibits MDMA-induced hyperthermia mainly by blocking the activation of 5-HT(2A) receptors.     

发热及低体温大鼠下丘脑腺苷酸环化酶和磷酸二酯酶活性的经时变化

目的和方法：采用放射性同位素法观察发热和低体温大鼠下丘脑腺苷酸环化酶（AC）及磷酸二脂酶（PDE）活性的经时变化。结果：鲜酵母皮下注射后4 h引起体温明显升高（P<0.01）,并长时维持在高位水平,AC活性在造模后3 h达峰值（P<0.05）,其后活性下降并渐至正常,PDE活性在整个过程中略有上升;安痛定腹腔注射后15 min动物即呈现低体温状态（P<0.01）,AC活性15 min时有一短暂上扬后至45 min降到最低点（P<0.05）,之后活性逐步回升,而PDE活性则在正常水平上下小幅波动。结论：下丘脑AC活性的增强可能是动物体温升高的重要因素,而PDE活性并未相应显著升高则又造成了体温长时的偏高;在低体温模型中,AC活性的明显下降表明cAMP可能与动物的低温状态有关。     

发热及低体温大鼠下丘脑中腺苷酸环化酶活性与环一磷酸腺苷含量的变化

目的和方法:采用放射性同位素法观察发热和低体温大鼠下丘脑中腺苷酸环化酶(AC)活性与cAMP含量的经时变化。结果:(1)鲜酵母皮下注射后4h引起体温明显升高(P＜0.01),并长时间维持在高位水平,AC活性在造模后3h达峰值(P＜0.05),其后活性迅速下降,历3h又再度上扬超出正常水平(P＜0.01);cAMP含量的变化是由低渐高,且与体温的变化趋势相似。(2)安痛定腹腔注射后15min动物即呈现低体温状态(P＜0.05),在造模后45minAC活性及cAMP含量均降至最低点(P＜0.05),其后AC活性及cAMP含量均逐步回升至正常水平。结论:(1)在发热模型中,下丘脑AC活性的增强使细胞内cAMP含量增多是动物体温升高的重要原因。(2)在低体温模型中,AC活性的明显下降以及cAMP含量的明显减少表明cAMP与动物的低温状态有关,但降温的始动环节不依赖于cAMP。     

Oxidative stress is enhanced by hypothermia imposed on cerulein-induced pancreatitis in rats

BACKGROUND: Hypothermia is a frequent event in severe acute pancreatitis (AP) and its real effects on the normal pancreas have not been well demonstrated. Moreover, neither have its effects on the outcome of acute pancreatitis been fully investigated. One hypothesis is that oxidative stress may be implicated in lesions caused or treated by hypothermia. AIM OF THE STUDY: To investigate the effect of hypothermia in cerulein-induced acute pancreatitis (CIAP) in rats and the role played by oxidative stress in this process. METHODS: Male Wistar rats were divided into hypothermic and normothermic groups. Hypothermia was induced with a cold mattress and rectal temperature was kept at 30 masculineC for one hour. Acute pancreatitis was induced with 2 doses of cerulein (20 ìg/kg) administered at a one-hour interval. Serum amylase, pancreas vascular permeability by Evan's blue method, pancreas wet-to-dry weight ratio and histopathology were analyzed in each group. RESULTS: When compared with normothermic rats, hypothermic animals, with cerulein-induced acute pancreatitis, showed higher levels of pancreatic vascular permeability (p < 0.05), pancreas wet-to-dry weight ratio (p = 0.03), and histologically verified edema (p < 0.05), but similar serum amylase levels. The hypothermic group showed a higher oxidized-reduced glutathione ratio than the normothermic group. CONCLUSION: Moderate hypothermia produced a greater inflammatory response in established acute pancreatitis induced by cerulein in rats. Moreover, this study suggests that oxidative stress may be one of the mechanisms responsible for the worse outcome in hypothermic rats with cerulein-induced acute pancreatitis.     

-5℃低温对大鼠睾丸生精作用及性激素水平的影响

目的探讨低温对睾丸结构和功能的影响.为低温应用于男性抗生育提供科学依据.方法将大鼠睾丸温度降至-5℃,在降温后不同时段采用光镜、组织化学方法观察睾丸生精细胞、间质细胞、支持细胞的形态学变化,并测定血清性激素水平. 结果低温作用于大鼠睾丸后,对精子发生和成熟有迅速干扰作用,并且是可逆的.对支持细胞和睾丸间质细胞无明显损伤,性激素水平正常.结论提示低温作为一种男性抗生育方法是可行的.