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41.
Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis 总被引:7,自引:0,他引:7
Assunta Imperato Stefano Puglisi-Allegra Paola Casolini Luciano Angelucci 《Brain research》1991,538(1):111-117
Microdialysis was employed to assess extracellular dopamine from medial prefrontal cortex, nucleus accumbens, nucleus caudatus, and acetylcholine from the hippocampus of conscious rats during and after 120 min restraint stress. Restraint stress rapidly stimulated the release and the metabolism of dopamine in the medial prefrontal cortex and in the nucleus accumbens, and acetylcholine release in the hippocampus. Fifty-sixty min later, although rats were still restrained, dopamine and acetylcholine release gradually returned to basal levels. When the animals were freed a considerable increase in the release of both neurotransmitters was observed. No changes in the striatum were observed throughout the experiments. The time-course of plasma corticosterone did not parallel that of dopamine and acetylcholine release, increasing during the whole stress procedure, and decreasing when the animals were released. Adrenalectomized rats responded to stress and liberation in much the same way as intact rats. The administration of exogenous corticosterone (0.5-1.5 mg/kg s.c.) did not change the release of dopamine from the prefrontal cortex and nucleus accumbens, and of acetylcholine from the hippocampus, while the dose of 3.0 mg/kg which stimulated them, raised plasma corticosterone to very high concentrations which had never been attained during stress. Moreover, RU 38486, an antagonist of brain glucocorticoid receptors, did not antagonize the stress-induced increase of neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
42.
目的 探讨 RU4 86抗子宫内膜增生作用对雌激素背景的依赖性。方法 选择 10例人正常增生期子宫内膜 ,分别在 17β-雌二醇、RU4 86及两者并存的培养基中进行培养。Ki- 6 7作为细胞增生活性的标记物用免疫组化方法测定。结果 腺上皮细胞 Ki- 6 7积分 (3.90± 1.37)明显高于基质细胞 Ki- 6 7积分 (2 .6 0± 0 .93)。单纯 RU4 86无明显抗内膜增生活性 (P>0 .0 5 ) ;17β-雌二醇显著增加腺上皮 Ki- 6 7积分 (6 .30± 1.95 ) ,而 17β-雌二醇与 RU4 86联合处理后 ,腺上皮 Ki- 6 7积分显著下降至 2 .30± 0 .6 8(P<0 .0 1) ,而对基质细胞 Ki- 6 7积分无影响。结论 RU4 86与雌激素共同作用部位是子宫内膜腺上皮细胞 ,RU4 86能阻断雌激素的刺激作用 ,其抗增生活性依赖于雌激素背景的存在 相似文献
43.
Pharmacological stimuli decreasing nucleus accumbens dopamine can act as positive reinforcers but have a low addictive potential 总被引:2,自引:0,他引:2
Michela Marinelli Michel Barrot Hervé Simon Claude Oberlander Anne Dekeyne Michel Le Moal Pier Vincenzo Piazza 《The European journal of neuroscience》1998,10(10):3269-3275
Opioid peptides, through μ and δ receptors, play an important part in reward. In contrast, the role of κ receptors is more controversial. We examined the possible positive reinforcing effects of a selective κ agonist, RU 51599, by studying intravenous self‐administration in the rat. The effect of RU 51599 on dopamine release in the nucleus accumbens was also studied, as opioids and dopamine seem to interact in the mediation of reward. The behavioural and dopaminergic effects of RU 51599 were compared with those of the μ agonist heroin. Rats self‐administered both RU 51599 (6.5, 20 and 60 μg/inj) and heroin (30 μg/inj) at low ratio requirement. When the ratio requirement, i.e. the number of responses necessary to receive one drug infusion, was increased, self‐administration of RU 51599 rapidly extinguished, whereas self‐administration of heroin was maintained. Intravenous infusion of RU 51599 (100, 200 and 400 μg) dose‐dependently decreased (25, 30 and 40%, respectively) extracellular concentrations of dopamine, as measured by means of microdialysis in freely moving rats. In contrast, heroin increased accumbens dopamine (130% over baseline). These results indicate that κ receptors, similarly to μ ones, can mediate positive reinforcing effects of opioid peptides. However, the strength of the reinforcement is very low for κ receptors. This suggests that changes in accumbens dopamine do not correlate with the capacity of a stimulus to induce reward or aversion. In contrast, a parallel seems to exist between an increase in accumbens dopamine and the drive to reach or obtain a positive reinforcer. 相似文献
44.
D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine 总被引:3,自引:0,他引:3
A study was performed to examine behavioral response to a challenge of selective dopamine D-1 and D-2 agonists in rats previously sensitized by subchronic administration of methamphetamine or cocaine. Rats in three groups received repeated injections (IP) of saline, methamphetamine (4 mg/kg/day) or cocaine (20 mg/kg/day), respectively, for 14 days. After an abstinence period of 7–13 days, all groups were challenged with either a selective D-1 agonist (SKF 38393) or D-2 agonists (quinpirole or RU 24213). The ability of SKF 38393 (6 mg/kg or 18 mg/kg) to produce grooming behavior did not differ significantly among the saline-, methamphetamine-and cocaine-treated groups. In contrast, quinpirole (1 mg/kg) and RU 24213 (3 mg/kg) produced more intense stereotypy consisting of rearing, sniffing and repetitive head movement in the two psychostimulant-treated groups than in the saline-treated group. Such augmented response to selective D-2 agonists was observed even after a 1-month abstinence period. These results suggest that the enduring behavioral sensitization induced by two pharmacologically distinct psychostimulant agents, methamphetamine and cocaine, occurs through a common neurobiological mechanism of lasting supersensitivity in postsynaptic D-2, but not D-1 dopamine receptors. 相似文献
45.
Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens 总被引:2,自引:0,他引:2
Antiandrogens are in use alone and in combination with other agents as hormonal therapy for prostate cancer. We conducted studies on the androgen-responsive human prostate cancer cell line LNCaP to determine the direct effects of three antiandrogens (hydroxyflutamide, RU23908, and cyproterone acetate) on hormone-responsive human prostate cancer cells in culture. Dihydrotestosterone (DHT) stimulated the growth of LNCaP cells in a dose-dependent fashion. These cells contained approximately 31,000 high-affinity (Kd = 9 x 10(-10) M) androgen binding sites per cell. In the absence of any androgenic stimulation, all three antiandrogens tested showed agonistic properties by increasing the cell number and uptake of [3H]-thymidine. Competitive uptake studies using [3H]-R1881, a nonmetabolized androgen, showed that the three antiandrogens inhibited specific R1881 uptake with IC50s of 0.9 x 10(-7) M for hydroxyflutamide, 2 x 10(-7) M for RU23908, and 1 x 10(-7) M for cyproterone acetate. It is not known whether these unexpected agonistic effects are due to an altered receptor, previously unmasked agonistic properties of the antiandrogens, or emergence of a hypersensitive clone of cells. 相似文献
46.
RU486是一种新型抗孕激素催经止孕药。本文对其进行Ames、染色体畸变及微粒等三项体内外遗传毒性试验。结果Ames及染色体畸变试验无论代谢活化与否,RU486均呈阴性反应;微核试验中,即使RU486用量为1.2g╱kg 24h后(临床用量的400倍)亦不引起小鼠骨髓多染微核率增加。提示RU486无遗传毒性作用。 相似文献
47.
Rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the ascending nigro-striatal pathway have been shown to rotate in response to dopamine (DA) agonists that are not considered to have postsynaptic DA stimulant properties in intact animals, suggesting a relative loss of DA receptor selectivity in the denervated striatum. The present experiments assessed the possibility that this loss of selectivity may extend to serotonin (5HT) agonist drugs. The 5HT-1a agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at doses of 0.3–3 mg/kg SC, induced robust contralateral rotational behavior (RB) in 6-OHDA-lesioned rats that had been preselected on the basis of high responsiveness to the atypical DA agonists 3-PPP and SKF 38393. Rats with unilateral dorsal raphe lesions induced by 5,7-dihydroxytryptamine (5,7-DHT) showed contralateral RB in response to similar doses of 8-OH-DPAT but with a different behavioral pattern. The putative 5HT-1b agonist RU 24969 produced contralateral RB in 5,7-DHT-lesioned rats while showing a much weaker effect in 6-OHDA-lesioned rats. Striatal DA levels were depleted by 99% in representative 6-OHDA-lesioned rats but striatal 5HT levels were unaffected. The effects of 8-OH-DPAT in 6-OHDA-lesioned rats were therefore not attributable to destruction of ascending 5HT-containing neurons. These effects may result from indirect actions, mediated by 5-HT neurons or neuronal receptors, that result from asymmetry of brain DA systems. Alternatively, it is proposed that rats with highly denervated striatal DA receptors show a loss of apparent molecular selectivity such that weak partial DA agonist properties of 8-OH-DPAT, although not demonstrable in normal rats, become manifested under these conditions.
Offprint requests to: J.M. Liebman 相似文献
48.
J. FICHELLE E. NALINE J.L. FRESLON S. JOUQUEY G. PLASSARD M.A. THOMPSON P. MILLER and C. ADVENIER 《Fundamental & clinical pharmacology》1988,2(6):525-540
The bronchodilator properties of RU 42173, a new beta-adrenergic stimulant with an original structure, as a cyclic analogue of an arylethanolamine, have been evaluated on different in vitro and in vivo models and compared with those of salbutamol and isoprenaline. RU 42173 equipotently inhibited histamine-, acetylcholine-, and KCl-induced contractions in isolated guinea pig trachea or small bronchus and in isolated human bronchus. When administered to guinea pigs by the IV or aerosol route, RU 42173 dose-dependently inhibited bronchospasm induced by histamine, acetylcholine, and methacholine. It also inhibited PAF-induced bronchoconstriction and PAF-induced hyperreactivity to histamine. Moreover, RU 42173 had a rapid onset and prolonged duration of action. The potency of RU 42173 was similar to that of salbutamol. 相似文献
49.
Pretreatment with the antiemetic agent trimethobenzamide (TMB) prevented the hypophagic response of rats to acetyl salicylate
(a known emetic in man and dogs). However, it did not affect the hypophagic responses to the 5-HT1B agonist RU 24969, or to the 5-HT1C/5-HT1B agonistsmCPP and TFMPP. The results therefore suggest that the hypophagic effects of the 5-HT agonists do not involve a malaise-dependent
mechanism similar to that mediating the effect of acetyl salicylate. 相似文献
50.
Inhibition of sexual behavior in female guinea pigs by a progestin receptor antagonist 总被引:2,自引:0,他引:2
The new steroidal progestin receptor antagonist, RU 38486, was used to determine if progesterone-facilitation of sexual behavior in female guinea pigs requires interaction of the hormone with neural progestin receptors. Five milligrams but not 0.5 mg RU 38486 inhibits the expression of sexual behavior in ovariectomized, estrogen-primed guinea pigs treated with 0.1 mg progesterone. This inhibition can be overcome by administration of a large dose of progesterone, suggesting that the drug-effect is specific to the progestin receptor system. RU 38486 binds, in vitro, to progestin receptors and decreases the availability of hypothalamic progestin receptors in estrogen-treated guinea pigs. These studies provide strong evidence that progesterone interaction with intracellular neural progestin receptors mediates the facilitation of sexual behavior by progesterone in female guinea pigs. 相似文献