Orexins在雌性大鼠条件性蔗糖摄取中的作用研究

目的:探讨Orexins在雌性大鼠的摄取蔗糖的操作反应行为的作用,以及在线索诱导下恢复寻找蔗糖行为中的作用。方法:将雌性SD大鼠分为限制进食组和自由进食组,以固定比率和累进比率训练大鼠自己摄取蔗糖颗粒。通过Ox R1受体拮抗剂SB-334867预处理,观察SB-334867对大鼠按固定比率摄取蔗糖行为和在线索诱导下恢复寻找蔗糖行为的影响。结果:限制进食的大鼠表现出按压有效杠杆次数和获取蔗糖颗粒数显著增多(P0.05),按压无效杠杆次数稍微增多。SB-334867可显著减少限制进食大鼠按压有效杠杆次数(P0.05)。与对照组相比,SB-334867在消退期间可显著增加按压有效杠杆的次数(P0.05);在恢复期间,限制进食大鼠按压有效杠杆的次数显著增多(P0.05)。结论:Orexins系统在大鼠条件刺激诱导摄取蔗糖中可能存在性别差异。     

Progestins and place preference conditioning after paced mating

When female rats pace their coital interaction, a reward state evaluated by conditioned place preference is induced. Progesterone (P) is essential for the expression of proceptive behavior and for the induction of CPP. However, the functional significance of ring A reduction of P for the induction of this state during estrous is unsettled. In the present study, we evaluated whether ring A-reduced metabolites of P are involved in the reward state induced when the females are allowed to pace their sexual contacts. Ovariectomized (ovx) female rats treated with estradiol benzoate (EB, 5 microg) and P (13 microg), Megestrol acetate (MA; 13 microg ), 5 alpha-pregnan-20 dione (5 alphaDHP; 3 microg), or 5 beta-pregnan-3 alpha-ol-20-one (5 beta,3 alpha-Pgl; 3 microg) were used. Progestins were dissolved in propylene glycol and intravenously (iv) injected through an indwelling jugular catheter before females were tested for pacing behavior. After 15 intromissions or one ejaculation, females were gently placed in the nonpreferred compartment of a CPP box. Paced mating in all groups treated with progestins induced a clear change of preference. The administration of progestins alone did not induce CPP. These results suggest that P and ring A-reduced metabolites facilitate the reward state following pacing.     

Repeated administration of LiCl produces an unconditioned stimulus preexposure effect in backward excitatory CTA but not habituation of the unconditioned increment in neophobia

In one experiment using conditioned taste aversion and the unconditioned stimulus (US) preexposure procedure, one group of rats was given LiCl exposure for 3 days, whereas two other groups received saline. Following this phase, all groups were given a novel flavour (saccharine) to drink following either LiCl (group preexposed and one of the control groups) or saline injections (the remaining control group) and the consumption of the flavour was assessed. After this neophobia test, the acquired saccharine aversion was evaluated. The results show that three LiCl injections are enough to produce a US preexposure effect on backward excitatory taste aversion conditioning, whereas this number of injections procedure does not produce habituation of the increment in neophobia, an unconditioned response to the LiCl. The results are discussed taking into account different mechanisms involved in US preexposure effect.     

Antipsychotic profile of 5-[2-[4-(6-fluoro-1H-indole-3-yl)piperidin-1-yl]ethyl]-4-(4-fluorophenyl)thiazole-2-carboxylic acid amide (NRA0562) in rats

The antipsychotic profile of 5-[2-[4-(6-fluoro-1H-indole-3-yl)piperidin-1-yl]ethyl]-4-(4-fluorophenyl)thiazole-2-carboxylic acid amide (NRA0562) was investigated using the conditioned avoidance test in rats. NRA0562 is a putative "atypical" antipsychotic agent with moderate to high affinities for dopamine D(1), D(2), D(4), 5-hydroxytryptamine(2A) receptors and alpha(1) adrenoceptor. NRA0562 (1 and 3 mg/kg, p.o.) dose-dependently and significantly impaired the conditioned avoidance response. Likewise other atypical antipsychotics such as risperidone (1 and 3 mg/kg, p.o.) and clozapine (100 mg/kg, p.o.) dose-dependently and significantly impaired the conditioned avoidance response in rats. In addition, typical antipsychotics, haloperidol (1 and 3 mg/kg, p.o.) potently impaired the conditioned avoidance response.These results suggest that antipsychotic profile of NRA0562 is consistent with profiles of clozapine or risperidone and may be considered an atypical antipsychotic agent.     

Secreted factors from adipose tissue-derived mesenchymal stem cells suppress oxygen/glucose deprivation-induced cardiomyocyte cell death via furin/PCSK-like enzyme activity

Clinical application of mesenchymal stem cells (MSCs) represents a potential novel therapy for currently intractable deteriorating diseases or traumatic injuries, including myocardial infarction. However, the molecular mechanisms of the therapeutic effects have not been precisely revealed. Herein, we report that conditioned media (CM) from rat adipose tissue-derived MSCs (ASCs) protected adult cardiomyocytes from oxygen/glucose deprivation (OGD)-induced cell death. We focused on furin/PCSK protease activity in ASC-CM because many therapeutic factors of MSCs and soluble cardioprotective factors include the PCSK cleavage site. We found that recombinant furin protected cardiomyocytes from OGD-induced cell death. The ASC-CM had potent furin/PCSK protease activity and the cardioprotective effect of the CM from ASCs in the OGD-assay was abolished by an inhibitor of the furin/PCSK-like enzyme. Microarray analysis and Western blot analysis showed PCSK5A, the secreted type of PCSK5, is the most abundantly secreted PCSK among 7 PCSK family members in ASC. Finally, knockdown of PCSK5A in ASCs decreased both the furin/PCSK protease activity and cardioprotective activity in the CM. These findings indicate an involvement of furin/PCSK-type protease(s) in the anti-ischemic activity of ASCs, and suggest a new mechanism of the therapeutic effect of MSCs.     

Comparing test–retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli

This study aimed to compare the reliability and magnitude of conditioned pain modulation (CPM) by applying different test stimuli (TS) and conditioning stimuli (CS). Twenty-six healthy male participants were recruited in the study of two identical sessions. In each session, four TS (electrical, heat, handheld, and cuff pressure algometry) were applied before and during CS (cold pressor test (CPT) or cuff algometry). The same procedure was repeated with 45-min intervals, but with the other CS. Five thresholds were measured including four pain detection thresholds from four TS and pain tolerance threshold from cuff TS (cuff PTT). Intraclass correlation coefficient (ICC (3,1)) and coefficient of variation (CV) were calculated as measures of reliability. The reliability of TS before and during CS was good for all combinations (ICC: 0.60–0.96, CV: 2.2–22.9%), but the reliability of the CPM effect varied (ICC: 0.04–0.53, CV: 63.6–503.9%). The most reliable combinations were considered to be the handheld pressure pain threshold with CPT (ICC: 0.49, CV: 63.6%) and the cuff pressure pain threshold with CPT (ICC: 0.44, CV: 107.6%). Significant CPM effects were found for all combinations, except the combinations of electrical and heat pain thresholds with cuff CS, which indicates the novel classification of the CPM mechanism. The combinations of handheld pressure and heat pain threshold with CPT would provide the minimum sample size to detect the significant CPM changes in further studies. It is beneficial to provide and compare both ICC and CV to design further clinical trials.     

Inhibitory conditioning for carrot somatic embryogenesis in high-cell-density cultures

Carrot somatic embryogenesis was strongly inhibited in high-cell-density cultures. This inhibition was not caused by depletion of nutrients or physical damage but by factor(s) released into the culture medium from cells during culture. A conditioned medium prepared by eliminating cells after high-cell-density culture inhibited somatic embryogenesis. The degree of inhibition increased with the amount of conditioned medium. A dialysis experiment revealed that the molecular weight of the inhibiting factor(s) was below 3,500. We also found that the conditioned medium contained a high-molecular-weight factor(s), which stimulated somatic embryogenesis. Received: 13 March 1998 / Revision received: 19 May 1998 / Accepted: 1 June 1998     

Administration of a 5HT3 receptor antagonist increases the intake of diets containing Eucalyptus secondary metabolites by marsupials

The effect of a naturally occurring plant phenolic constituent (the acylphloroglucinol derivative, jensenone, derived from Eucalyptus jensenii) on the food intake of two folivorous marsupials, the common ringtail (Pseudocheirus peregrinus) and the common brushtail possum (Trichosurus vulpecula) was studied. When fed diets containing varying concentrations of jensenone, both species regulated their intake of jensenone so as not to exceed a ceiling intake. This ceiling was about twice as high for common ringtails as for common brushtails from northern Australia. Southern populations of common ringtails showed greatly reduced capacities to tolerate jensenone. When common brushtails were injected (0.5 mg · kg^−0.75 body mass) with ondansetron (a selective antagonist of serotonin 5HT₃ receptors), they ate significantly more jensenone than animals injected with physiological saline. The same pattern was observed when common ringtails were fed diets containing both jensenone and ondansetron (0.0035 mg · g⁻¹ wet mass of diet). Ondansetron injection had no effect on food intake when the food did not contain jensenone while the addition of higher doses of ondansetron to diets of common ringtails very slightly reduced food intakes of a non-jensenone diet. When common brushtails were given 50 mg of jensenone by gastric lavage, their average subsequent intake of dietary jensenone matched the difference between the daily threshold and the dose given, although the response of individuals was highly variable. Lavage with water alone had no effect on subsequent jensenone intake compared with the pre-dose period. We interpret these results as evidence that the antifeedant effects of jensenone and related compounds are partly mediated by serotonin action on 5HT₃ receptors most likely via “nausea” to condition a food aversion. Accepted: 6 August 1998     

Effects of the Serotonin1A Agonist, 8-Hydroxy-2-(Di-n-Propylamino)tetralin on Neurochemical Responses to Stress

Abstract: The effects of intracerebroventricular administration of the 5-hydroxytryptamine (5-HT)_1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 pmol) on adrenocortical and neurochemical responses to stress were examined in conscious male rats. The following stress paradigms were used: acoustic stimulation (105 dB for 2 min); footshock (0.2 mA, five shocks over 5 min); conditioned fear (animals placed in a footshock chamber for 5 min, 24 h after footshock); restraint (5 min); intraperitoneal (i.p.) injection of recombinant human interleukin-1α (rHu-IL-1α, 20 µg/kg); and injection of cocaine hydrochloride (20 mg/kg, i.p.). As previously shown, 8-OH-DPAT was able to attenuate the adrenocortical response to acoustic stress, conditioned fear, rHu-IL-1α, and cocaine administration. Cocaine decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT and dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios and norepinephrine (NE) concentration in the prefrontal cortex, hypothalamus, and brainstem in all experiments, and 8-OH-DPAT reversed the changes in DOPAC/DA ratio without affecting 5-HIAA/5-HT ratios or NE content. 8-OH-DPAT alone had no effect on these parameters, although it decreased NE content in the prefrontal cortex in several experiments, and in the brainstem in one experiment. Significant decreases in NE content were observed in some brain regions following some of the stressors, but these changes were not generally affected by 8-OH-DPAT. Increases in the 5-HIAA/5-HT and DOPAC/DA ratios were also observed in some brain sites following some stressors, but these changes were not affected by 8-OH-DPAT except in the case of the increased 5-HIAA/5-HT ratio in the prefrontal cortex following the conditioned fear response. These results indicate that although 8-OH-DPAT is able to decrease plasma corticosterone responses following acoustic stress, conditioned fear, rHu-IL-1α, and cocaine administration, these effects do not appear to be related to an action of the 5-HT_1A agonist on biogenic amine metabolism. This observation indicates that the predominant effect of 8-OH-DPAT on adrenocortical responses is mediated at postsynaptic sites not involved in the regulation of cerebral biogenic amine metabolism.     

Secretome from hypoxia-conditioned adipose-derived mesenchymal stem cells promotes the healing of gastric mucosal injury in a rodent model

Studies have indicated that the definitive engraftment and transdifferentiation potential of stem cells do not seem crucial for its property of tissue repair. Our previous study showed that transplantation of adipose-derived mesenchymal stem cells (ADMSCs) enhanced the healing of sutured gastric perforation. This study aimed to investigate the paracrine role of ADMSCs in the experimental gastric mucosal injury. Normoxia-conditioned medium (Nor CM) and hypoxia (HPO) CM were obtained after culturing ADMSCs in 20% O₂ and 5% O₂ for 48 h. Cell migration, proliferation, viability, and angiogenesis in vitro were significantly enhanced upon incubation with CM, especially the HPO CM. Experiments in vivo using a rodent model of gastric ulcer demonstrated that HPO CM treatment significantly accelerated wound healing by suppressing inflammation and promoting neovascularization and re-epithelization. Meanwhile, the infusion of HPO CM activated the COX₂-PGE₂ axis both in vitro and in vivo. And the upregulation of COX₂ was further dependent on the activation of ErK1/2-MAPK pathway. In addition, vascular endothelial growth factor, tissue inhibitors of metalloproteinases-1, and chemokine (C-C motif) ligand 20 (CCL-20) were analyzed as being highly abundant factors secreted by ADMSCs under hypoxic condition. Notably, the blockade of CCL-20 abrogated the HPO CM-induced COX₂ signaling in the primary gastric mucosal epithelial cells, while incubation with recombinant CCL-20 increased the expression of COX₂. In conclusion, the secretome from hypoxia-conditioned ADMSCs facilitates the repair of gastric mucosal injury through the enhancement of angiogenesis and re-epithelization, as well as the activation of COX₂-PGE₂ axis with a paracrine activity involving CCL-20 factor.