scholarly journals A comparative study of the new xylarate germanium (IV) complexe with lithium (xygerm-1), lithium chloride and valproic acid to the amphetamine-enhanced self-stimulation reactions in rats

2013 ◽  
Vol 94 (3) ◽  
pp. 344-349
Author(s):  
E I Varbanets ◽  
V V Godovan ◽  
A A Shandra ◽  
O A Kaschenko

Aim. To estimate the effect of novel lythium bis(µ-xylarato)dihydrogermanate (IV) (Xygerm-1) on reinforcing properties of the lateral hypothalamus self-stimulation in rats compared to the reference drugs (lithium chloride and valproic acid) in rats with amphetamine-induced self-stimulation. Methods. To form a model of the brain self-stimulation, nichrome monopolar electrodes were implanted bilaterally in the lateral hypothalamic nucleus, followed by morphological control, and 7-10 days after the operation, the rats were trained to press a pedal for electrical stimulation of the brain. The effects of self-stimulation were assessed by analyzing the maximum rate of pedal pressing and the self-stimulation threshold. Study of the test compounds effects had been started when average self-stimulation threshold values varied by less than 10% for three consecutive sessions of the brain self-stimulation. Xygerm-1 (300-1800 mg/kg), valproic acid (30-300 mg/kg) and lithium chloride (25-200 mg/kg) were introduced as intraperitoneal injections to animals of the corresponding study groups (6 rats each). At the next stage of the experiment, effects of Xygerm-1, lithium chloride and valproic acid on amphetamine-induced (dose 0.5 mg/kg) brain self-stimulation reaction increase were studied at the same animal groups. Results. At the first stage of the experiment Xygerm-1 (1200 and 1800 mg/kg), lithium chloride (100 and 200 mg/kg) and valproic acid (300 mg/kg) had significantly increased self-stimulation threshold. High doses of Xygerm-1 and lithium chloride (1800 and 200 mg/kg correspondingly) had relevantly decreased the average self-stimulation rate. There was also a tendency for the average self-stimulation rate to decrease in animals administered valproic acid, though, not statistically significant. The use of Xygerm-1 and lithium chloride induced the dose-dependant self-stimulation threshold increase, decreased by the use of amphetamine sulfate. Rather high doses of Xygerm-1 and lithium chloride (1800 and 100 mg/kg correspondingly) had also blocked amphetamine-induced increase in pedal pressing rate. Studied doses of valproic acid did not altered the amphetamine-induced brain self-stimulation reaction increase. Conclusion. The novel compound bis(µ-xylarato)dihydrogermanate (IV) has a strong influence on behavior, in particular on the brain reward systems, which is similar to the action of lithium chloride and differs from the effect of valproic acid.

1971 ◽  
Vol 29 (2) ◽  
pp. 655-665 ◽  
Author(s):  
Irmingard I. Lenzer

The effects of two concurrently changing drive variables, food deprivation and estrogen level, on the self-stimulation rate in the hypothalamus, septum, caudate nucleus, or dorsal hippocampus of 15 female albino rats were studied. When the effects of hunger were calculated using only scores on days of diestrus and the effects of estrogen were calculated using only scores on days of 0-hr. food deprivation, the correlation of these hunger and estrogen effects amounted to 0.67. When the hunger effects were calculated using only scores on days of estrus and these hunger effects correlated with the previously calculated estrogen effects, the correlation amounted to −0.49. These results are consistent with the concept of diffuse overlapping motivational systems in the brain. Controls indicated that the changes in self-stimulation rate were not artifacts of changes in nonspecific activity.


2020 ◽  
Vol 17 (4) ◽  
pp. 57-64
Author(s):  
Petr D. Shabanov ◽  
Sergei V. Azarenko ◽  
Vitalii I. Morozov ◽  
Yulia N. Bessolova ◽  
Andrei A. Lebedev

Purpose. In experiments on rats, we studied the self-stimulation reaction of the lateral hypothalamus and the conditioned reaction of place preference upon activation (orexin) and blockade of the orexin receptor by SB-408124 or Orexin B18-28 in rats. Methods. As behavioral methods, self-stimulation of the lateral hypothalamus and a conditioned reaction of place preference were chosen. Orexin and its antagonists SB-408124 or Orexin B18-28 (Sigma, USA) were used for pharmacological analysis. All preparations were used in 3 dosages: 0.1, 1.0, 10 g, injecting into the lateral ventricle of the brain (i.v.) through the implanted cannula. Results. It has been shown that peptide substances of orexin and its antagonists modulate the conditional and unconditional reinforcing properties of the brain. The studied orexin antagonists showed a dose-dependent (0.1-1-10 g, i.v.) inhibitory effect on the self-stimulation of the lateral hypothalamus, activated by indirect adrenergic agonist amphetamine (-phenylisopropylamine). The inhibitory effect of orexin antagonists also manifested itself in relation to the generation and expression of a preference for amphetamine place, especially when using high doses of the peptide (10 g i.v.). Conclusion. The effect of orexin antagonists can be used in the development and study of antinarcotic drugs.


2006 ◽  
Author(s):  
Katie M. Albanos ◽  
Steve Reilly ◽  
Justin R. St. Andre

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.


2021 ◽  
Vol 22 (2) ◽  
pp. 759
Author(s):  
Karen P. Briski ◽  
Mostafa M. H. Ibrahim ◽  
A. S. M. Hasan Mahmood ◽  
Ayed A. Alshamrani

The catecholamine norepinephrine (NE) links hindbrain metabolic-sensory neurons with key glucostatic control structures in the brain, including the ventromedial hypothalamic nucleus (VMN). In the brain, the glycogen reserve is maintained within the astrocyte cell compartment as an alternative energy source to blood-derived glucose. VMN astrocytes are direct targets for metabolic stimulus-driven noradrenergic signaling due to their adrenergic receptor expression (AR). The current review discusses recent affirmative evidence that neuro-metabolic stability in the VMN may be shaped by NE influence on astrocyte glycogen metabolism and glycogen-derived substrate fuel supply. Noradrenergic modulation of estrogen receptor (ER) control of VMN glycogen phosphorylase (GP) isoform expression supports the interaction of catecholamine and estradiol signals in shaping the physiological stimulus-specific control of astrocyte glycogen mobilization. Sex-dimorphic NE control of glycogen synthase and GP brain versus muscle type proteins may be due, in part, to the dissimilar noradrenergic governance of astrocyte AR and ER variant profiles in males versus females. Forthcoming advances in the understanding of the molecular mechanistic framework for catecholamine stimulus integration with other regulatory inputs to VMN astrocytes will undoubtedly reveal useful new molecular targets in each sex for glycogen mediated defense of neuronal metabolic equilibrium during neuro-glucopenia.


2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.


Polymers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1431
Author(s):  
Fadzai P. Mutingwende ◽  
Pierre P. D. Kondiah ◽  
Philemon Ubanako ◽  
Thashree Marimuthu ◽  
Yahya E. Choonara

Nanotechnology has aided in the advancement of drug delivery for the treatment of several neurological disorders including depression. Depression is a relatively common mental disorder which is characterized by a severe imbalance of neurotransmitters. Several current therapeutic regimens against depression display drawbacks which include low bioavailability, delayed therapeutic outcome, undesirable side effects and drug toxicity due to high doses. The blood–brain barrier limits the entry of the drugs into the brain matrix, resulting in low bioavailability and tissue damage due to drug accumulation. Due to their size and physico-chemical properties, nanotechnological drug delivery systems present a promising strategy to enhance the delivery of nanomedicines into the brain matrix, thereby improving bioavailability and limiting toxicity. Furthermore, ligand-complexed nanocarriers can improve drug specificity and antidepressant efficacy and reduce drug toxicity. Biopolymers and nanocarriers can also be employed to enhance controlled drug release and reduce the hepatic first-pass effect, hence reducing the dosing frequency. This manuscript reviews recent advances in different biopolymers, such as polysaccharides and other nanocarriers, for targeted antidepressant drug delivery to the brain. It probes nano-based strategies that can be employed to enhance the therapeutic efficacy of antidepressants through the oral, intranasal, and parenteral routes of administration.


1979 ◽  
Vol 51 (5) ◽  
pp. 587-596 ◽  
Author(s):  
Albert N. Martins ◽  
Ralph E. Severance ◽  
James M. Henry ◽  
Thomas F. Doyle

✓ The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1½ days before and 10½ days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of dexamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.


Neurosurgery ◽  
1988 ◽  
Vol 22 (3) ◽  
pp. 454-464 ◽  
Author(s):  
Ken R. Winston ◽  
Wendell Lutz

Abstract A new system has been developed for stereotactically delivering prescribed high doses of radiation to precisely located volumes of approximately 0.6 to 10.0 ml within the brain. A Brown-Roberts-Wells stereotactic apparatus and a 6-MeV linear accelerator equipped with a special collimator (12.5 to 30 mm in diameter) have been adapted. The 20-mm collimator allows treatment of a nearly spherical volume of 2.1 ml. Outside the treatment field, the dosage declines to 80% of the dose prescribed for the periphery of the lesion over a distance of 1.8 mm and to 50% over the next 3.4 mm. Localization can be accomplished via computed tomography or cerebral angiography. Treatment is accomplished with an arcing beam of photon radiation with the turntable (couch) in each of four positions. The entire system has been extensively tested for accuracy in alignment and distribution of radiation. Errors have been measured for the alignment of the apparatus and for the process of localization. Safety of operation was emphasized throughout the design and testing phase. (Neurosurgery 22:454-464, 1988)


2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


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