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1.
The effects of idazoxan, a novel antidepressant that is a potent and selective α(2)-adrenoceptor antagonist, were studied on sleep. Twelve normal male volunteers had sleep recordings made using the Oxford ambulatory system (Medilog 9000) with subsequent analysis by automatic sleep staging and visual inspection. Idazoxan was given in a dose of 40 mg three times a day for 21 days. Sleep recording on day 3 demonstrated markedly reduced indices of rapid eye movement (REM) sleep, although other sleep parameters were only minimally affected. The effect on REM persisted unchanged at day 18, however on the second day after withdrawal a rebound in REM measures was observed. These data show that idazoxan has an effect on sleep which is very similar to that of other antidepressants, and emphasize a role for noradrenaline in the regulation of REM sleep. 相似文献
2.
Smith AP Wilson SJ Glue P Nutt DJ 《Journal of psychopharmacology (Oxford, England)》1992,6(3):376-381
Idazoxan, an α( 2)-adrenoceptor antagonist, is an effective antidepressant with a mode of action different from that of conventional antidepressants. As it is used as an antidepressant it is important to know whether there are any unwanted CNS side effects. Study of its effects will also provide information on the relationship between noradrenergic function and mood and performance. Twelve normal male volunteers who were given the drug (40 mg orally three times daily for 21 days) were compared with 12 matched controls. A computerized test battery was used to assess mood and various aspects of memory and attention. Many of the tests of memory and attention in the battery have been widely used over the last 20 years, and in addition two new selective attention tasks were included. The subjects were tested 3 days before starting the drug, on days 3 and 17 while on the drug, and after they had stopped taking the drug (4 days after and 24 days after). Control subjects followed a similar testing schedule. The results showed that the drug had no effect on mood, logical reasoning, retrieval from semantic memory or sustained attention. However, the drug did improve one aspect of selective attention (the place repetition effect), although this effect was only observed on the third day on the drug. Overall, the results suggest that idazoxan produces selective performance improvements, and that the measures of selective attention used here may be more sensitive indicators of drug effects than some of the traditional tasks currently in use. 相似文献
3.
The object of the experiment was to verify whether cannabidiol (CBD) reduces the anxiety provoked by
9-TCH in normal volunteers, and whether this effect occurs by a general block of the action of
9-TCH or by a specific anxiolytic effect. Appropriate measurements and scales were utilized and the eight volunteers received, the following treatments in a double-blind procedure: 0.5 mg/kg
9-TCH, 1 mg/kg CBD, a mixture containing 0.5 mg/kg
9-TCH and 1 mg/kg CBD and placebo and diazepam (10 mg) as controls. Each volunteer received the treatments in a different sequence. It was verified that CBD blocks the anxiety provoked by
9-TCH, however this effect also extended to marihuanalike effects and to other subjective alterations induced by
9-TCH. This antagonism does not appear to be caused by a general block of
9-TCH effects, since no change was detected in the pulse-rate measurements. Several further effects were observed typical of CBD and of an opposite nature to those of
9-TCH.These results suggest that the effects of CBD, as opposed to those of
9-TCH, might be involved in the antagonism of effects between the two cannabinoids.With a fellowship from Capesfrom CNPq 相似文献
4.
RATIONALE: Inability to tolerate delays to reward is an important component of impulsive behaviour, and has been suggested to reflect dysfunction of dopamine systems. OBJECTIVES: The present experiments examined the effects of signalling a delayed, large reward on rats' ability to choose it over a small, immediate reward, and on the response to amphetamine, a dopamine receptor antagonist, and a benzodiazepine. METHODS: Three groups of Lister hooded rats were tested on a two-lever discrete-trial delayed reinforcement task in which they chose one pellet delivered immediately or four pellets delivered after a delay. This delay increased from 0 to 60 s during each session. Trials began with illumination of a houselight: in the Houselight group, this remained on during the delay and feeding period. In the No Cue group, the houselight was extinguished at the moment of choice. In the Cue group, a stimulus light was illuminated during the delay. Once trained, the rats were challenged with d-amphetamine (0.3, 1.0, 1.6 mg/kg), chlordiazepoxide (1.0, 3.2, 5.6, 10 mg/kg), alpha-flupenthixol (0.125, 0.25, 0.5 mg/kg), and various behavioural manipulations. RESULTS: Subjects' choice became and remained sensitive to the delay; the cue speeded learning. Amphetamine decreased choice of the large reinforcer in the No Cue group and increased it in the Cue group. alpha-Flupenthixol and chlordiazepoxide generally decreased preference for the delayed reinforcer; flupenthixol reduced the cue's effects, but chlordiazepoxide did not interact with the cue condition. CONCLUSIONS: Signals present during a delay can enhance the ability of amphetamine to promote choice of delayed rewards. 相似文献
5.
Acute treatment of rats either by high doses of morphine or 9-tetrahydrocannabinol (THC) decreased locomotor activity. Naloxone reversed morphine-induced depression completely and reversed THC-induced depression only partially. On day 3 of treatment, tolerance developed to the locomotor inhibitory action of THC or morphine and partial cross-tolerance was observed to the depressant action of THC. Naloxone slightly depressed locomotor activity in THC-tolerant rats, but increased motor activity in morphine-tolerant rats. 相似文献
6.
目的:建立测定生长激素(GH)在体生物活性的方法.方法:以去垂体大鼠体重增长(BWG)和胫骨骺软骨板宽度(TEW)为指标,观察动物性别、给药途径、次数和周期不同对效应的影响;同时进行4dBWG,6dBWG和6dTEW法,测定GH的效价(平行线3×3设计).结果:♀和♂sc和im给药以及每日给药1次和2次的BWG和TEW差异无显著意义.给药6d比给药4d引起较大的BWG和TEW(P<005).4dBWG法和6dBWG法在0020-0500IU·d-1有较好的λ值(00660和01747)和r值(09000和09237);4dBWG,6dBWG和6dTEW法测得rhGH的效价为46132,39829和48023IU/amp.6dBWG法有较小的λ值和较低的ARFL值.结论:可在同一组去垂体大鼠体内同时用4dBWG,6dBWG和6dTEW法测GH活性,以6dBWG法较好. 相似文献
7.
Wang HL Chen XT Yin ST Liu J Tang ML Wu CY Ruan DY 《Naunyn-Schmiedeberg's archives of pharmacology》2008,378(3):303-310
Among the developmental changes identified in rats exposed to lead are impairments in long-term potentiation (LTP) in the hippocampus and changes in the levels of reactive oxygen species (ROS) in cells and some soft tissues. alpha-Lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead-induced oxidative stress. To explore the effects of LA on LTP in chronically lead-exposed rats and the relationship between ROS and LTP in both control and lead-exposed rats, we have compared LTP and oxidative stress parameters in groups of lead-exposed and control rats with or without LA treatment (10, 25, 50, and 100 mg/kg through intraperitoneal injection). The capacity of LA to decrease hippocampal lead levels in lead-exposed rats was examined. We found that LA had no effects in decreasing the level of lead in the hippocampus, but it did appear to have both antioxidant properties and a reparatory effect on LTP amplitude in rats developmentally exposed to lead for 2 weeks following birth. Interestingly, bell-shaped dose-response curves emerged. In the lower LA dosage groups (10, 25 mg/kg LA), there was an increasing LTP amplitude. The strongest protective effect in terms of the induction and amplitude of LTP in the lead-exposed group with at 25 mg/kg LA; when higher dosages were applied (50, 100 mg/kg LA), the LTP amplitude decreased as compared to the 25 mg/kg LA treatment group. The administration of LA to control animals resulted in a significant impairment of LTP amplitude, with the 100 mg/kg LA treatment having harmful effects on the oxidative parameters. These differential effects of LA on LTP in control and lead-exposed rats may be due to the different redox status of the control and lead-exposed rats. 相似文献
8.
《European journal of pharmacology》1985,112(2):243-247
α-Adrenoceptor number and function were examined in brain, platelets, and other peripheral tissues of young (2–3 months) and mature (6–8 months) non pregnant female rabbits. α1-Adrenoceptor number was significantly higher in forebrain, hindbrain, spleen and heart of mature rabbits. α2-Adrenoceptor number, on the other hand, was found to be significantly lower in platelets, forebrain and spleen but not changed in hindbrain and kidney of mature animals compared to young females. There was a significant reduction in platelet aggregation with maturation. However, no change in in vivo pressor or depressor responses to α-adrenoceptor agonists was observed in vivo. 相似文献
9.
YUJuan ZHOUYu QIULi-Ying CHENBai-Ling CHENChong-Hong 《中国药理通讯》2004,21(2):41-42
AIM : To study the protective effects and the mechanisms of rofecoxib as a specific type 2 cyclooxygenase (COX- 2 inhibitor on focal cerebral ischemia reperfusion injury ( CIRI in rats. METHODS : The model of focal CIRI was induced by reversible middle cerebral artery occlusion ( MCAO with inserting a thread through internal carotid artery, 2 h occlusion followed 相似文献
10.
Baicalein and breviscapine are traditional Chinese medicines and are extensively used in clinic to treat cardiovascular diseases and cerebrovascular injury. In a series of studies, we demonstrated that both of them have therapeutic effects on cognitive impairment and neuronal degeneration in a rat model of chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO). 相似文献
11.
M. A. Aleixandre M. Puerro A. Pintado 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(5):500-506
TMB-8 has been characterized as an inhibitor of the release of Ca+ from intracellular pools. We have studied the modification of the pressor responses to selective l-adrenoceptor agonists (methoxamine and phenylephrine), and to selective 2-adrenoceptor agonists (B-HT 920 and B-HT 933) in pithed rats, produced by TMB-8. We have compared this modification with that produced by the calcium antagonist nifedipine. Nifedipine (100 g/kg, 300 g/kg, and 1000 g/kg) inhibited in a dose-dependent manner the pressor responses to the 1- and 2-adrenoceptor agonists, the dose-response curves to the 2-adrenoceptor agonists being shifted further to the right. TMB-8 at a dose of 3000 g/kg did not modify the pressor effects of the l-adrenoceptor agonists, and neither did it reinforce the inhibition of such responses produced by nifedipine. By contrast, TMB-8 pretreatment (0.03 g/kg, 0.3 g/kg, 3 g/kg, 30 g/kg, 300 g/kg and 3000 g/kg) inhibited the responses to both 2-adrenoceptor agonists, the inhibition being more pronounced with B-HT 920. A similar effect was obtained with 0.03 g/kg TMB-8 and 0.3 g/kg TMB-8, particularly in the case of B-HT 920. It was stronger with higher doses, but similar for all doses over 3 g/kg. The inhibition of the pressor responses mediated by the stimulation of 2-adrenoceptors by TMB-8 was less in rats treated with the Ca2+ entry promoter BAY K 8644 (300 g/kg), and could also be reduced by the continuous infusion of CaCl2 (0.25 g/min). These results suggest that in pithed rats TMB-8 may also behave as an inhibitor of the Ca+ influx into vascular smooth muscle. 相似文献
12.
目的:研究赛庚啶(Cyp)对大鼠垂体甲状腺轴和胰岛β细胞内分泌功能的影响.方法:用放射免疫测定法及生化分析法观察赛庚啶对大鼠垂体甲状腺轴和胰岛β细胞内分泌功能的影响.结果:Cyp23mg·kg-1,ig10d,使大鼠血清TSH、胰岛素含量均降低,而T3、T4及血糖水平无明显改变.Cyp46mg·kg-1引起血清TSH、T3、T4和胰岛素含量显著降低,血糖水平明显升高;垂体TSH细胞和胰岛β细胞的超微结构亦发生不同程度的退行性变化.结论:Cyp对垂体甲状腺轴和胰岛β细胞的内分泌功能有抑制作用 相似文献
13.
Rationale Overall drug acceptability is thought to be a function of the balance between its rewarding and aversive effects, the latter
of which is reportedly affected by polydrug use.
Objectives Given that nicotine and alcohol are commonly co-used, the present experiments sought to assess nicotine’s impact on ethanol’s
aversive effects within a conditioned taste aversion design.
Materials and methods Experiment 1 examined various doses of nicotine (0, 0.4, 0.8, 1.2 mg/kg) to determine a behaviorally active dose, and experiment
2 examined various doses of ethanol (0, 0.5, 1.0, 1.5 g/kg) to determine a dose that produced intermediate aversions. Experiment
3 then examined the aversive effects of nicotine (0.8 mg/kg) and ethanol (1.0 g/kg) alone and in combination. Additionally,
nicotine’s effects on blood alcohol concentrations (BAC) and ethanol-induced hypothermia were examined.
Results Nicotine and ethanol combined produced aversions significantly greater than those produced by either drug alone or the summed
aversive effects of the individual compounds. These effects were unrelated to changes in BAC, but nicotine and ethanol combined
produced a prolonged hypothermic effect which may contribute to the increased aversions induced by the combination.
Conclusions These data demonstrate that nicotine may interact with ethanol, increasing ethanol’s aversive effects. Although the rewarding
effects of concurrently administered nicotine and ethanol were not assessed, these data do indicate that the reported high
incidence of nicotine and ethanol co-use is unlikely due to reductions in the aversiveness of ethanol with concurrently administered
nicotine. It is more likely attributable to nicotine-related changes in ethanol’s rewarding effects. 相似文献
14.
15.
Ventral hippocampal α7 and α4β2 nicotinic receptor blockade and clozapine effects on memory in female rats 总被引:1,自引:0,他引:1
Rationale Nicotinic systems in the hippocampus play important roles in memory function. Decreased hippocampal nicotinic receptor concentration is associated with cognitive impairment in schizophrenia and Alzheimer’s disease.Methods We modeled in rats the cognitive effects of chronic decrease in hippocampal α7 or α4β2 receptors with 4-week continuous bilateral local infusions of the α7 nicotinic antagonist methyllycaconitine (MLA) or the α4β2 antagonist dihydro-β-erythroidine (DHβE). The working memory effects of these infusions were assessed by performance on the radial-arm maze. To test the effect of antipsychotic medication, we gave acute injections of clozapine and to determine the impact of nicotine, which is widely used by people with schizophrenia approximately half of the rats received chronic systemic infusions of nicotine.Results Chronic ventral hippocampal DHβE infusion caused a significant (p<0.001) working memory impairment. Acute systemic clozapine (2.5 mg/kg) caused a significant (p<0.005) working memory impairment in rats given control aCSF hippocampal infusions. Clozapine significantly (p<0.025) attenuated the memory deficit caused by chronic hippocampal DHβE infusions. Chronic ventral hippocampal infusions with MLA did not significantly affect the working memory performance in the radial-arm maze, but it did significantly (p<0.05) potentiate the memory impairment caused by 1.25 mg/kg of clozapine. Chronic systemic nicotine did not significantly interact with these effects.Conclusions The state of nicotinic receptor activation in the ventral hippocampus significantly affected the impact of clozapine on working memory with blockade of α7 nicotinic receptors potentiating clozapine-induced memory impairment and blockade of α4β2 receptors reversing the clozapine effect from impairing to improving memory. 相似文献
16.
Kyrillos N. Adesina-Georgiadis Nicola Gray Robert S. Plumb David F. Thompson Elaine Holmes 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(11):1352-1359
Abstract1. The metabolic fate and urinary excretion of 2-bromophenol, a phenolic metabolite of bromobenzene, was investigated in male Sprague–Dawley rats following single intraperitoneal doses at either 0, 100, or 200?mg/kg.2. Urine was collected for seven days and samples analysed using 1?H NMR spectroscopy, inductively coupled plasma (ICP)MS, and UPLC-MS.3. 1?H NMR spectroscopy of the urine samples showed that, at these doses, 2-bromophenol had little effect on endogenous metabolite profiles, supporting histopathology and clinical chemistry data, which showed no changes associated with the administration of 2-bromophenol in this study.4. The use of ICP-MS provided a means for the selective detection and quantification of bromine-containing species and showed that between 15 and 30% of the dose was excreted via the urine over 7?days of the study for both the 100 and 200?mg doses, respectively.5. The bulk of the excretion of Br-containing material had occurred by 8?h post administration. UPLC-MS of urine revealed a number of metabolites of 2-bromophenol, with 2-bromophenol glucuronide and 2-bromophenol sulphate identified as the major species. A number of minor hydroxylated metabolites were also detected as their glucuronide, sulphate, or O-methyl conjugates. There was no evidence for the production of reactive metabolites. 相似文献
17.
The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and -methyl-p-tyrosine (-MPT). BRC (1–20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5–20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), -MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus -MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC), a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy. Furthermore, haloperidol (0.02 and 1.0 mg/kg IP), sulpiride (20 mg/kg IP) or scopolamine (0.5 mg/kg IP) inhibited BRC-induced yawning, but prazosin (1.0 and 3.0 mg/kg IP), an -1 receptor antagonist, did not affect this behavior. These results suggest that BRC-induced yawning may be mediated via presynaptic dopaminergic neuron activity and that BRC, in addition to the stimulation of dopamine D-2 receptors, appears to require endogenous dopamine or receptor activation by another dopamine agonist (D-1 agonist) for the induction of yawning, stereotypy and upright fighting responses. The ability of dopamine agonists to induce these behaviors seems to depend apon the potency and ratio of D-2 versus D-1 receptor activity. 相似文献
18.
This study examined the protective effects of icariin (ICA) on the learning and memory deficits in Aluminium (Al) -treated rats and potential mechanisms. The screened, qualified rats were treated with 1. 6 g/L AlCl3 in drinking water for 8 months, and the ability of spatial learning and memory was tested by Morris water maze. Aluminium (Al) administration significantly increased the mean escape latency searching distance in place navigation test, and decreased the searching time in the quadrant once the platform was in space probe test and adjusted searching distance in space probe test, indicative of brain spatial learning and memory deficits. ICA treatment (60, 120 mg/kg, i. g 3 month) significantly protected against Al-induced spatial learning and memory deficits, as evidenced by decreased escape latency and searching distance, and by increased the searching time in the quadrant once the platform was adjusted via searching distance compared with the Al alone group. To examine the mechanisms of the protection, the activities of superoxide dismuase (SOD) and the contents of maloidaldehyde (MDA) in hippocampus were assayed by commercial kits, and the level of Aβ1-40 in hippocampus was examined by immunohistochemistry (IHC), respectively. ICA treatment significantly increased the activities of SOD, decreased the content of MDA and the level of Aβ1-40 in hippocampus in a dose - dependent manner. In summary, this study demonstrates that ICA is effective in improving the ability of spatial learning and memory of Al-intoxicated rats. 相似文献
19.
Objective: To investigate the effects of repeated seizures induced experimentally on emotional memory in rats. Methods :Two experimental models of epilepsy were used in the rats : (a) pentylenetetrazol-kindling seizure, an animal models of human absence epilepsy and myoclonic or generalized tonic-clonic seizures ; (b) amygdaloid - kindling seizure, an animal model of human complex partial epilepsy with secondary generalized seizure. One week after full kindled, 相似文献
20.
Milić M Divljaković J Rallapalli S van Linn ML Timić T Cook JM Savić MM 《Behavioural pharmacology》2012,23(2):191-197
Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of γ-aminobutyric acid A (GABAA) receptors containing α1 and α5 subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the α1-selective agonist zolpidem, as well as nonselective, α1-subunit and α5-subunit-selective antagonists flumazenil, βCCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10 mg/kg) and βCCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by βCCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that α1 GABAA receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas α5 GABAA receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia. 相似文献