Effect of L-dopa on emotional responses and serotonin metabolism in the rat brain

Experiments on male Wistar rats showed that injection of L-dopa in doses of 100–200 mg/kg causes a parallel increase in the dopamine and homovanillic acid concentrations in the brain, elevation of the 5-hydroxyindoleacetic acid level, and a decrease in the serotonin concentration. Increased emotional reactivity and aggressiveness of the animals was observed at the same time. L-dopa (100 mg/kg) reduced the binding of serotonin formed from tryptophan (100 mg/kg) and accelerated its catabolism in the brain. At the same time, L-dopa abolished the depressant effect of tryptophan on emotional reactivity and aggressiveness. It is suggested that inhibition of the serotoninergic system in the brain is an essential component of the mechanism of strengthening of emotional responses under the influence of L-dopa.Department of Pharmacology, Tartu University. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 134–137, February, 1976.     

Genetic differences in the synthesis and reception of noradrenaline in the mouse brain and behavior in a novel environment

The activity of tyrosine hydroxylase, the key enzyme in catecholamine biosynthesis, was studied along with adrenoceptor density in the brains of male CBA/Lac, BALB/cLac, and C57BL/6J mice, which show different responses to novel environments. C57BL mice showed the highest level of movement activity and the lowest level of emotionality in a novel environment. Mice of this line also showed the highest brainstem tyrosine hydroxylase activity. At the same time, the density of β-adrenoceptors in the cortex and hypothalamus of C57BL mice was ower than in the other two lines of mice, while the density of α₂-adrenoceptors in these parts of the brain was lower than in CBA mice. In BALB mice, movement activity was twice as high as in CBA mice, while levels of emotionality were similar in these two lines. Tyrosine hydroxylase activity was higher in the cerebral cortex of BALB mice, while the density of α₂-adrenoceptors was lower than in CBA mice. These results show that increased investigative activity and decreased emotionality were seen in animals with higher levels of noradrenaline synthesis and decreased density of adrenergic receptors in the brain. Translated from Rosiikii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 1, pp. 105–109, January, 1999.     

KATP通道开放剂对新生大鼠缺氧缺血后大脑 μ-calpain活化、c-Fos和c-Jun表达的影响

目的:探讨ATP敏感钾通道(K_ATP)开放剂二氮嗪(diazoxide)对新生大鼠缺氧缺血性脑损伤(HIBI)后皮层和海马μ-calpain活化、c-fos和c-jun蛋白(c-Fos,c-Jun)表达的影响。方法:采用新生7 d龄SD大鼠复制HIBI模型,分别在缺氧缺血(HI)前、后侧脑室注射diazoxide 5 μL(1 g/L)。采用Western blot法检测皮层和海马HI后4 h c-Fos和c-Jun蛋白条带的积分光度值(ID)及24 h μ-calpain两个活性片段(76/80 kD)的ID比值。结果:HI对照组皮层和海马c-Fos和c-Jun的ID值显著高于正常对照组;HI前给药组显著低于HI对照组(P<0.01);HI后给药组也较HI对照组低(P<0.05)。HI前、后给药均能抑制HI后μ-calpain的裂解,降低两个活性片段的比值。结论:K_ATP通道开放剂diazoxide可能通过降低c-Fos和c-Jun的表达、抑制μ-calpain的活化,起到对HIBI的拮抗及治疗作用。     

Behavioral peculiarities and reactions of brain dopaminergic systems in rats with different resistance to acute hypobaric hypoxia

Locomotor activity in the open field test did not correlate with rat resistance to acute hypobaric hypoxia; there was a correlation between this resistance and rat behavior during acute stress. Immobility was characteristic of rats with low and particularly medium resistance to hypoxia; this reaction can be abolished by antidepressants. by contrast, highly resistant rats were mainly hyperactive. The resistance to hypoxia was associated with extreme parameters of dopaminergic neuron functioning. In low-resistant rats locomotor stereotypia was maximal, while perioral stereotypia was the minimal; highly resistant rats were characterized by an opposite pattern, and medium-resistant rats occupied an intermediate position.     

Effect of cardiac glycosides on RNA content in cardioregulatory structures of the hind brain

Department of Pharmacology, Leningrad Pediatric Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. N. Golikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 1, pp. 49–50, January, 1990.     

Protein metabolism of rat brain synaptosomes during training

The intensity of metabolism of proteins with fast and slow turnover from cerebral cortical synaptosomes of rats trained in defensive movements, pseudotrained, and control animals was studied by determining their specific radioactivity 1 and 3 days, and 1, 3, 6, and 9 weeks after intraventricular injection of lysine-¹⁴C. Three fractions of synaptosomal proteins, differing in the overall values of their half-life (_{5 0}) were found. An increase was found in the specific radioactivity of brain proteins of the trained animals compared with those of the pseudotrained and control rats. Values of _{5 0} were increased for the slowly metabolized fraction of synaptosomal protein fractions from the brain of the trained rats. The role of protein metabolism in brain synapses in the mechanisms of formation of long-term memory is discussed.Department of Physiology, Medico-Biological Faculty, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 259–260, March, 1980.     

Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers

Opiate addiction is a chronic medical disorder characterized by drug tolerance and dependence, behavioral sensitization, vulnerability to compulsive relapse, and high mortality. In laboratory animals, the potential effect of opiate drugs to induce cell death by apoptosis is a controversial topic. This postmortem human brain study examined the status of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of a large group of well-characterized heroin or methadone abusers. In these subjects (n=36), the immunocontent of apoptosis-1 protein (Fas) death receptor did not differ from that in age-, gender-, and postmortem delay-matched controls. In contrast, Fas-associated protein with death domain (FADD), the mediator of the death signal, was significantly decreased in the same brain samples (all addicts: 30%, n=36; short-term abuse (ST): 31%, n=15; long-term abuse (LT): 29%, n=21). The initiator caspase-8 was not altered, but FLIP(L) (Fas-associated protein with death domain-like interleukin-1beta-converting enzyme-inhibitory protein), a dominant inhibitor of caspase-8, was increased in LT addicts (19%). In the intrinsic pathway, the pro-apoptotic mitochondrial proteins Bax (Bcl-2-associated X protein) and AIF (apoptosis-inducing factor) remained unchanged, but cytochrome c was decreased (all addicts: 25%; ST: 31%; LT: 20%) and anti-apoptotic B-cell leukemia 2 (Bcl-2) increased in LT addicts (24%). The content of executioner caspase-3 and the pattern of cleavage of the nuclear enzyme poly-(ADP-ribose)-polymerase-1 (PARP-1) were similar in opiate addicts and control subjects. Taken together, the data revealed that the extrinsic and intrinsic canonical apoptotic pathways are not abnormally activated in the prefrontal cortex of opiate abusers. Instead, the chronic modulation of some of their components (downregulation of FADD and cytochrome c; upregulation of FLIP(L) and Bcl-2) suggests the induction of non-apoptotic actions by opiate drugs related to phenomena of synaptic plasticity in the brain. These neurochemical adaptations could play a major role in the development of opiate tolerance, sensitization and relapse in human addicts.     

乙醇处理与大鼠脑内多巴胺能体系的关系

目的观察乙醇处理大鼠脑内酪氨酸羟化酶(TH)和多巴胺转运体(DAT)的表达变化,判断乙醇对脑内多巴胺(DA)能体系的影响。方法选取Wistar大鼠60只,随机分为对照组和乙醇处理组,每组30只,乙醇处理组大鼠以20%乙醇代替饮水饲养6个月;利用免疫组织化学、流式细胞术及免疫印迹等方法,分析乙醇处理大鼠有关脑区TH和DAT的表达改变。结果1.免疫细胞化学法研究发现,乙醇处理组大鼠脑内黑质(SN)-腹侧被盖区(VTA)、尾壳核(CPu)和伏核(NACC)TH的灰度值明显低于对照组(P0.05);尾壳核和伏核DAT的灰度值明显低于对照组(P0.05)。2.流式细胞术检测发现,乙醇处理组大鼠中脑TH的表达量明显高于对照组(P0.05)。3.免疫印迹检测发现,乙醇处理组大鼠所观察脑区TH和DAT与β-actin条带相对吸光度比值明显高于对照组(P0.05)。结论乙醇处理增加大鼠脑内TH和DAT的表达。     

Effect of catecholamines on the activity of rat brain dipeptidyl aminopeptidase

The inhibitory effect of catecholamines, their metabolic intermediates and derivatives on the activity of rat brain dipeptidyl aminopeptidase was studied. The enzyme was extracted from a crude mitochondrial fraction containing lysosomes (and also synaptosomes) and purified by three-step column chromatography. The activity of the purified enzyme was inhibited by a low concentration (IC50 2 approximately 5 mM) of dopamine, norepinephrine and epinephrine. Dihydroxyphenylalanine or dihydroxyphenylacetic acid, each having a carboxyl group, showed only a weak inhibitory effect (IC50 greater than 10 mM). These results suggest the possibility that brain dipeptidyl aminopeptidase activity may be regulated by the changing of the concentration of catecholamines in the central nervous system.     

Cytophotometric study of ATPase activity in brain neurons and gliocytes of paradoxical sleep-deprived rats

Conditions were chosen for optimal demonstration of ATPases in brain slices by a modified method of Wachstein and Meisel, and the reaction was shown to obey the Bouguer-Beer laws, confirming that ATPase activity can be determined quantitatively in single cells by cytophotometry. In rats in a state of relative physiological rest specific activity of both Na⁺, K⁺-ATPase and Mg⁺⁺-ATPase in gliocytes of the hippocampus and dorsal raphe was found to be considerably higher than in neurons. Deprivation of the paradoxical phase of sleep of the rats for 24 h led to a significant increase in Na⁺, K⁺-ATPase activity in hippocampal neurons and to a decrease in its activity in gliocytes of the hippocampus and dorsal nucleus raphe. It is suggested that these changes in Na⁺, K⁺-ATPase activity may be due to some extent to a change in excitability of neurons and depolarization of the glia when sleep is disturbed.Translated from Fiziologicheskii Zhurnal SSR imeni I. M. Sechenova, Vol. 74, No. 4, pp. 490–496, April, 1988.     

Effect of long-term hypokinesia on monoamine system and antioxidant status of the brain

Long-term hypokinesia (30 days) was accompanied by activation of the serotoninergic and dopaminergic systems. Exhaustion of the antioxidant system was observed on days 10-30 of immobilization.     

Macro- and microelectrophoretic investigation of constitutive proteins of brain structures

The protein composition of structures of the rat brain (premotor cortex, area CA3 of the hippocampus, caudate nucleus, frontal area of the cerebellum) was compared by macro- and microdisc electrophoresis. The protein zones were identified by their relative electrophoretic mobility, relative to the mobility of a marker protein (soy trypsin inhibitor). Both methods revealed no significant difference in the composition of the brain structures studied. Comparison of the results of electrophoretic fractionation of brain proteins indicates that the micromethod has greater resolving power.Laboratory of Physiological Mechanisms of Memory Control, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR N. P. Bekhtereva.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 11, pp. 556–559, November, 1977.     

Effects of electrical stimulation of rat limbic system and midbrain reticular formation upon short- and long-term memory

Rats were given electrical stimulation of the midbrain reticular formation, hippocampus or amygdala 4 sec after receiving a footshock contingent upon a barpress response. They were retested for memory of the shock 64 sec or 24 hr after the footshock. The animals that received midbrain reticular formation stimulation showed amnesia at 64-sec retest and memory at 24-hr retest. In contrast, animals that received hippocampal brain stimulation showed memory at 64-sec retest and amnesia at 24-hr retest. Animals that received amygdala brain stimulation showed amnesia at both 64-sec and 24-hr retest. The data support a dual parallel processing model of memory.