Dopamine Synthesis by Non-Dopaminergic Neurons in the Arcuate Nucleus of Rat Fetuses

The aim of the present work was to verify the hypothesis that non-dopaminergic neurons expressing individual complementary dopamine synthesis enzymes can perform the co-located synthesis of dopamine. According to this hypothesis, neurons expressing tyrosine hydroxylase use L-tyrosine for the synthesis of L-dihydroxyphenylalanine (L-DOPA), which then enters neurons expressing aromatic amino acid decarboxylase, which converts L-DOPA to dopamine. Experiments were performed using the mediobasal hypothalamus of rat fetuses, which mostly contains single-enzyme neurons (>99%) and occasional double-enzyme neurons (<1%). Controls were obtained from the fetal substantia nigra, which is enriched with dopaminergic neurons. High-performance liquid chromatography was used to measure levels of dopamine and L-DOPA in cell extracts and the incubation medium after incubation in the presence and absence of exogenous L-tyrosine. Addition of L-tyrosine to the medium led to increases in the level of synthesis and release of L-DOPA in the mediobasal hypothalamus and substantia nigra. In addition, L-tyrosine increased dopamine synthesis in the substantia nigra and decreased dopamine synthesis in the mediobasal hypothalamus. This regional difference in levels of dopamine synthesis is probably due to inhibition of the uptake of L-DOPA from the intercellular medium by neurons in the mediobasal hypothalamus containing aromatic amino acid decarboxylase, due to the competitive binding of the L-DOPA transporter by L-tyrosine. Thus, these results provide the first evidence for the co-located synthesis of dopamine by non-dopaminergic neurons expressing single complementary enzymes involved in the synthesis of this neurotransmitter.__________Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 90, No. 7, pp. 825–832, July, 2004.     

Development of brain stimulation reward in the medial prefrontal cortex: Facilitation by prior electrical stimulation of the sulcal prefrontal cortex

Electrical stimulation of the medial prefrontal cortex (MC) in rats delivered daily for seven days causes a marked improvement in the rate of acquisition of a self-stimulation response. In the present experiment, we looked at whether we could get the same facilitatory effect on self-stimulation of the MC by delivering pre-training stimulation to other points in the brain anatomically related to the MC. Electrical stimulation of the lateral hypothalamus was without effect. However, electrical stimulation of the sulcal prefrontal cortex (SC) either contralateral or ipsilateral to the MC electrode did facilitate acquisition of self-stimulation of the MC. Thus the SC and MC would appear to be part of the same substrate controlling the development of positive reinforcement in the MC.     

Effects of 9 -tetrahydrocannabinol and ethyl alcohol on adjunctive behavior and the lateral hypothalamus

The fact that electrical stimulation of the lateral hypothalamus (LH) can be substituted for the delivery of a food pellet in typical schedule induced polydipsia was established and demonstrated the role of this part of the brain in the mediation of adjunctive behavior. The assumption that Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and ethyl alcohol affect behavior because of a differential effect on the same LH mechanism was supported by the following evidence. Relatively small doses of Δ⁹-THC, 0.25, 0.375, and 0.50 mg/kg, enhanced adjunctive drinking; whereas, larger quantities of 0.625 and 0.75 mg/kg had no appreciable effects. The effect is somewhat specific, as it did not occur with strychnine sulfate, and rate dependent within limits as it was most pronounced in animals with low rates of responding or in animals when responding at a low rate. The effect of rate dependency was also apparent with fixed interval schedules of 2 and 4 min and a multiple schedule of a fixed interval and a signalled timed out period of nonreinforcement. Low rates of responding were enhanced by all doses of Δ⁹-THC, 1.0, 1.5, 2.0, 2,5, and 3.0 mg/kg, and there was an obvious dose related decrease in high rates. A similar effect was observed with low and high rates of electrical self-stimulation through implanted LH electrodes. The hypothesis that some drugs such as Δ⁹-THC and ethyl alcohol can enhance the positive feedback in an LH mediated motor control system by the facilitation of the same mechanism which initially generated the behavior was confirmed. Oral self administration of ethyl alcohol in a saccharin sweetened fluid enhanced recovered adjunctive drinking of the solution in quantities which should be sufficient to produce physical dependence if continued for relatively long periods. Recovered adjunctive drinking occurs in animals without food or water deprivation and it is an intense and persistent phenomenon.     

Factors influencing active avoidance behavior in rats with ventromedial hypothalamic lesions

Ventromedial hypothalamic lesioned rats maintained at preoperative body weight received an equal number of shocks while emitting significantly fewer responses than controls in a lever-pressing free-operant avoidance paradigm, and performed as well as unoperated animals in lever-pressing and shuttle box (both 1- and 2-way) discriminated avoidance tasks. The failure of VMH lesions to facilitate performance in the 2-way avoidance paradigm was probably the result of a ceiling effect. With the exception of the simple one-way avoidance task, obese lesioned rats were markedly impaired in the acquisition of all active avoidance behavior, but escape behavior was not affected. When tested in a free-operant paradigm, the avoidance performance of well trained lesioned animals varied inversely with body weight. As obese rats displayed lower flinch thresholds to shock than controls and similar levels of activity and responding as lean lesioned animals, it was concluded that their impaired avoidance behavior was not due to changes in sensitivity or mobility. The possible relation to other VMH lesion- and/or obesity-induced deficits is discussed.     

大鼠下丘脑到脊髓的直接纤维投射——WGA-HRP法研究

实验用28只170～285g SD大鼠。将WGA-HRP/HRP混合液注入颈、胸、腰及骶髓的一侧灰质。在下丘脑看到大量非均一性标记细胞。呈双侧分布,同侧较多;随着注射部位从头端向尾端移动,标记数量明显地递减。标记细胞以室旁核、下丘脑外侧区最为密集;视交叉后区、穹窿周核及未定带次之;下丘脑内侧区、室周核、背部下丘脑和后部下丘脑只有散在标记细胞;弓状核和视前区只有个别标记细胞。与文献相比,本实验表明,室旁核内的脊髓投射神经元并不局限于小细胞区,大细胞区也有较多分布;视上核和视交叉上核可能不直接投射到脊髓。     

Role of adrenergic innervation in regulation of secretory activity of cells of the rat supraoptic nucleus

To study the role of the noradrenergic innervation in the production of peptide neurohormones by cells of the supraoptic nucleus (SON) the substance 6-hydroxydopamine (6-HDA), which causes selective destruction of noradrenergic terminals, was used. The intensity of fluorescence of these terminals in the region of SON 7 days after intraventricular injection of 6-HDA in a dose of 250 g was sharply reduced and morphological pictures reflecting activation of hormone production by SON cells were observed. According to the results the noradrenergic innervation evidently inhibits synthesis of peptide neurohormones by SON cells and regulates the transport and secretion of peptide neurohormones from the posterior lobe of the pituitary into the general circulation.Laboratory of Neuroendocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 518–520, November, 1979.     

CCK and other peptides modulate hypothalamic norepinephrine release in the rat: Dependence on hunger or satiety

The purpose of this investigation was to determine the functional relationship between putative satiety peptides and endogenous norepinephrine (NE) activity in the hypothalamus. Permanent guide cannulae for push-pull perfusion were implanted stereotaxically in Sprague-Dawley rats so as to rest above the medial or lateral hypothalamus (LH). Post-operatively, the animals were either satiated with food and water, both available ad lib, or fasted for 18-22 hr prior to an experiment. To perfuse a site in the LH, paraventricular (PVN) or ventromedial nucleus (VMN), a concentric 29-23 ga push-pull cannula system was lowered to a pre-determined site, in most cases after catecholamine stores had been pre-labeled with [3H]-NE. During control tests, an artificial CSF was perfused at a rate of 20-25 microliter/min for 5-8 min with a 5 min interval between each sample. The addition of cholecystokinin (CCK) in a concentration of 2.0-6.0 ng/microliter to the CSF perfused in PVN or VMN of the satiated rat enhanced the efflux of NE; however, in the fasted animal CCK often suppressed the catecholamine's release. Perfused in the LH, CCK exerted opposite effects, typically augmenting NE output when the rat was fasted but not affecting the amine's activity during the sated condition. Proglumide (1.2 micrograms/microliter) attenuated CCK's effect in releasing NE when the antagonist was perfused in the PVN of the satiated rat. Similar experiments in which neurotensin (NT) was perfused in the LH, PVN and VMN revealed virtually the same inverse effects on NE release in the fasted and satiated rat, which again were anatomically specific. Finally, insulin and 2-deoxy-D-glucose (2-DG) exerted similar state-dependent effects on the release of NE within LH and PVN. Overall, the results suggest that CCK or other neuroactive peptide could serve as a "neuromodulator" of the pre-synaptic release of NE within classical hypothalamic structures which are thought to underlie both hunger and satiety. The state-dependent nature of the peptides' activity on the noradrenergic feeding mechanism implies that these substances constitute a pivotal portion of the profile of factors which impinge functionally upon the hypothalamic neurons responsible for the feeding response and its cessation.     

NO-cGMP通路对下丘脑钙激活钾通道的调控研究

目的研究一氧化氮（ＮＯ）对ＳＤ乳鼠下丘脑神经元钙激活钾（ＫＣａ）通道的作用及其机制。方法采用内面向外 式及细胞贴附式膜片钳技术比较浴槽液中加入１００μmol/L硝普钠（ＳＮＰ）前后动物下丘及神经元ＫＣａ通道动力学 的改变。结果细胞贴附式时浴槽液中加入１００μmol/L ＳＮＰ,通道开放概率由（７．３±１．５）％升高至（４０．２±６．５）％,开放时 间由（７．１２±１．４１） ｍｓ增大至（１５．３４±３．４５） ｍｓ,开放频率由（１１．３±３．５）Ｈz升高为（２６．６±４．２） Ｈz（ｎ＝１０, Ｐ＜０．０５）。结论 ＮＯ－cＧＭＰ通路可显著提高通道的开放概率,这种增强作用是通过延长通道开放时间及增加开放频率实现的,它的 病理或生理作用还有待于进一步研究。     

下丘脑与绝经后骨质疏松症的潜在关系

随着全球老龄化加剧,骨质疏松症的发病率逐年增加,尤其是女性骨质疏松症的发病人数占据首位,其中下丘脑作为调节中枢通过神经内分泌调节轴调控该疾病,而近年来有研究发现下丘脑中的某些部位和物质等也参与骨量的调节。因此,下丘脑成为研究绝经后骨质疏松机制和治疗的热点,有望从下丘脑中找到治疗绝经后骨质疏松的靶点。