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Introduction Dihydroergotamine (DHE) is a derivative of an ergot alkaloid used as an antimigraine medication. Nowadays, ergot alkaloids may still endanger the safety of humans and animals as food or medicine pollutants, but the outcomes of long-term DHE administration on the behaviour and neurotransmission remain undescribed. Material and methods Adult male Wistar Albino Glaxo rats pre-treated orally with DHE for six weeks were investigated to assess the relationship between concentration of neurotransmitters and behavioural response. The behavioural effects of the drug administered at doses of either 30 µg/kg b.w. (group DHE30, n = 11) or 100 µg/kg b.w. per day (group DHE100, n = 10) were evaluated in the Morris Water Maze. It is known that monoaminergic neurotransmitters (serotonin, noradrenaline and dopamine) in some brain structures (prefrontal cortex, hippocampus, striatum, cerebellum, spinal cord) play a role in the control of cognitive and motor functions. The concentration of neurotransmitters was determined by High Performance Liquid Chromatography (HPLC). Results Administration of DHE influenced neither the learning processes nor memory in rats. Nevertheless, an increased motor activity of the DHE-administered animals was observed in both the cued and non-cued behavioural tasks. In HPLC examination, changes in the concentration of monoaminergic neurotransmitters and their metabolites were noted in all tested structures, except for the hippocampus. Conclusions DHE is able to modulate noradrenergic, serotonergic and dopaminergic neurotransmission that may support the increase in locomotion.

This study aimed to investigate the influence of protocatechuic acid (PCA) on learning, memory, and central nervous system (CNS) neuromodulators in healthy rats, to analyse whether the procognitive effects of PCA found in animal models of memory impairment and described in the literature occur in healthy individuals.: PCA was administered: No obvious behavioural changes were observed. Post-mortem quantification of monoamines showed that the turnover of DA in the striatum was significantly increased by PCA. Moreover, hippocampal, and cortical levels of histidine were influenced by PCA and significantly decreased.: Despite many beneficial effects of PCA in experimentally developed cognitive impairments, it has no sharp effect on memory performance in healthy rats. The influence on the turnover of striatal DA and modulation of the amino acid system by affecting the concentration of histidine deserves a deeper examination due to the role of histamine in neuropsychiatric disorders as well as the functional interactions between histidine and DA metabolism in the brain.

The purpose of this research was to investigate the effects of protocatechuic acid (PCA) at doses of 50 and 100 mg/kg on the development of unfavourable changes in cognitive processes in a pyrithiamine-induced thiamine deficiency (PTD) model of the Wernicke–Korsakoff syndrome (WKS) in rats. The effects of PCA were assessed at the behavioural and biochemical levels. Behavioural analysis was conducted using the Foot Fault test (FF), Bar test, Open Field test, Novel Object Recognition test (NOR), Hole–Board test and Morris Water Maze test (MWM). Biochemical analysis consisting of determination of concentration and turnover of neurotransmitters in selected structures of the rat CNS was carried out using high-performance liquid chromatography. PTD caused catalepsy (Bar test) and significantly impaired motor functions, leading to increased ladder crossing time and multiplied errors due to foot misplacement (FF). Rats with experimentally induced WKS showed impaired consolidation and recall of spatial reference memory in the MWM test, while episodic memory related to object recognition in the NOR was unimpaired. Compared to the control group, rats with WKS showed reduced serotonin levels in the prefrontal cortex and changes in dopamine and/or norepinephrine metabolites in the prefrontal cortex, medulla oblongata and spinal cord. PTD was also found to affect alanine, serine, glutamate, and threonine levels in certain areas of the rat brain. PCA alleviated PTD-induced cataleptic symptoms in rats, also improving their performance in the Foot Fault test. In the MWM, PCA at 50 and 100 mg/kg b.w. improved memory consolidation and the ability to retrieve acquired information in rats, thereby preventing unfavourable changes caused by PTD. PCA at both tested doses was also shown to have a beneficial effect on normalising PTD-disrupted alanine and glutamate concentrations in the medulla oblongata. These findings demonstrate that certain cognitive deficits in spatial memory and abnormalities in neurotransmitter levels persist in rats that have experienced an acute episode of PTD, despite restoration of thiamine supply and long-term recovery. PCA supplementation largely had a preventive effect on the development of these deficits, to some extent also normalising neurotransmitter concentrations in the brain.

One of the reasons for using paracetamol during pregnancy is fever. The brain structure responsible for maintaining proper body temperature, but also for controlling some endocrine aspects is hypothalamus. In this study we examined the effect of early pretreatment of paracetamol on hypothalamic neurotransmission in rats’ offspring. We used two-month old rats previously exposed to paracetamol at doses of 5 (P5) and 15 mg/kg (P15) during gestational development and next postnatally. The concentration of monoamines, their metabolites and amino acids in hypothalamus was chromatographically determined. The results of biochemical analysis were compared with the Control animals (Con). We found differences between groups in the concentration of main noradrenaline metabolite in hypothalamus. The control group had significantly higher level of 3-methoxy-4-hydroxyphenylglycol (MHPG) compared with rats exposed to paracetamol (F(2,27) = 7.96, p These results demonstrated that paracetamol had a significant effect on dopaminergic and noradrenergic neurotransmission and changed the concentration of glutamic acid in hypothalamus - heat-regulating center and important element of hypothalamic-pituitary- gonadal axis.

In this study, we investigated the effects of early paracetamol treatment on the testicular level of testosterone and expression of genes important for steroid biosynthesis and reproduction in male rats offspring. Rats were continuously exposed to paracetamol at doses of 5 or 15 mg/kg b.w. during pregnancy and the first two months of the postpartum development. Testosterone level was determined by ELISA. Profile of gene expression for the testicular steroidogenic factors were evaluated using the Real-Time PCR. Our results showed that paracetamol reduces testicular testosterone level and causes compensatory transactivation of genes important for steroidogenesis and reproductive capacity. We have observed significant over-expression of several genes involved in cholesterol transport and steroid biosynthesis e.g., genes for steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, luteinizing hormone subunit beta, gonadotropin and androgen receptors. Up-regulation of these genes with parallel testosterone reduction in the testicles could be the possible mechanism that maintains and prevents the loss of the steroidogenic function.

Rooibos tea, brewed using Aspalathus linearis leaves, is a popular South African herbal infusion, but its everyday intake is not fully described in terms of the neuropsychopharmacological outcomes. The cell-protective activity of A. linearis is connected with the ability of reducing glycaemia, inflammation as well as oxidative stress. It was already shown that "fermented" rooibos herbal tea (FRHT), which is rich in phenolic compounds, improves the cognitive performance of rats in the water maze and impacts dopaminergic striatal transmission. The present research was taken to extend the knowledge about the feasible behavioural and neurochemical implications of sustained oral FRHT consumption. We hypothesized that it might affect brain amino acid content and thus induce behaviour and neuroprotection. FRHTs of different leaf to water ratios (1:100, 2:100 and 4:100), analysed by chromatographic methods as regards their flavonoid characteristics, were given to rats as only liquid for 3 months. Their behaviour was evaluated in the hole-board test (HBT). Brain amino acids concentration was analysed in the striatum, hippocampus and prefrontal cortex by HPLC-ECD. The rats drinking rooibos tea presented increased motor activity defined as time spent on moving in the HBT. Their exploration measured by head-dipping and rearing was enhanced. Longer time of the testing-box central zone occupation indicated to reduction in anxiety-related behaviour. Excitatory amino acids (aspartate and glutamate) content was decreased in the striatum of animals drinking the infusions whereas taurine level was increased both in the striatum and hippocampus. In conclusion we suggest that long-term FRHT intake affects exploration and anxiety-related behaviour of the rats as well as exerts biochemical outcomes in the brain that support the neuroprotective impact of rooibos tea.

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system.

Protocatechuic acid has very promising properties potentially useful in the inhibition of neurodegenerative diseases progression. It is the main metabolite of the complex polyphenolic compounds and is believed to be responsible for beneficial effects associated with consumption of the food products rich in polyphenols. Protocatechuic acid is present in the circulation significantly longer and at higher concentrations than parent compounds and easily crosses the blood brain barrier. The aim of the following paper is to provide an extensive and actual report on protocatechuic acid and its pharmacological potential in prevention and/or treatment of neurodegenerative diseases in humans based on existing data from both in vitro and in vivo studies. Experimental studies strongly support the role of protocatechuic acid in the prevention of neurodegenerative processes, including Alzheimer's and Parkinson's diseases, due to its favorable influence on processes underlying cognitive and behavioral impairment, namely accumulation of the β-amyloid plaques in brain tissues, hyperphosphorylation of tau protein in neurons, excessive formation of reactive oxygen species and neuroinflammation. There is a growing evidence that protocatechuic acid may become in the future efficacious and safe substance that protects against neurodegenerative disorders.

In the present study we examined the effect of prenatal and early life paracetamol exposure on neurotransmission and its behavioural manifestation in rat male pups. In order to assess the ability of spatial learning and memory consolidation and the level of physical and exploratory activity we conducted a series of behavioural tests: Staircase Test, Hole Board Test and Water Maze. The concentrations of monoamines, metabolites and amino acids were determined using High Performance Liquid Chromatography in the prefrontal cortex, hippocampus and striatum. The effect on spatial memory and exploratory behaviour was most pronounced in animals treated with the lower dose of paracetamol. In this group we have observed a much lower motor activity and decreased head-dipping behaviour. Simultaneously, the number of crossings in the Water Maze under the previous platform position during the probe trial was significantly higher in rats treated with paracetamol at the dose of 5mg/kg. There was also a preference for a new location of a platform to the original position of the platform in the reversal probe trial of this group. These results indicate that early paracetamol exposure produces major changes in serotonergic and dopaminergic neurotransmission in the prefrontal cortex and striatum. At the same time, administration of the drug in early life results in the spectacular change in the amino acid level, in particular in the hippocampus and cortex. This has been reflected in the behaviour of animals in the Water Maze and Hole Board Test (without any noticeable impact on the Staircase Test).

Ring shaped specimen is commonly used for determination of mechanical properties of artery in hoop direction. Such a method is very convenient due to easy preparation and fixing procedure of the sample. On the other hand the results obtained from that type of specimen might be inconclusive because of inappropriate strain calculation – it is hard to distinguish if the specimen starts to stretch already or is it still straightening up. To face these problems the authors proposed another approach, in which constitutive parameters are not determined directly from experimental stress-strain curve, but optimization procedure is used on a FE model of artery. Constitutive parameters are treated as a design variables and the goal is to minimize difference between experimental and numerical force-displacement curves. As the result of optimization procedure, the parameters of 2 nd order Ogden’s model were determined. The comparison of results shows that parameters obtained with the use of optimization describe characteristics of artery far better than parameters calculated directly from experimental data.

Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd.

Protocatechuic acid (PCA) is a phenolic compound believed to have neuroprotective and procognitive activity. d -Galactose (D-Gal) is a sugar, which administered to mammals can induce cognitive deficits. The first aim of this study was to confirm the effectiveness of D-Gal administered orally in inducing cognitive impairment in rats and describe how it affects the concentration of neurotransmitters in rats’ brain. The second aim was to evaluate the influence of PCA on learning, memory and neurotransmission in D-Gal-exposed rats. Memory impairment was induced by long-term administration of D-Gal (100 mg/kg body weight/day) directly via oral gavage. PCA (50 or 100 mg/kg body weight/day, respectively) was administered in drinking water. Morris Water Maze test (MWM) to assess learning and spatial memory was initiated after 38 days of treatment and lasted for 10 days. The concentrations of monoamines and their metabolites were evaluated in selected brain regions using high performance liquid chromatography. D-Gal significantly impaired cognitive performance during the acquisition and recall of MWM compared to control rats and changed concentrations of cortical serotonin as well as its cortical and hippocampal turnover. The turnover of dopamine was also influenced by D-Gal. Simultaneously, PCA was found to improve retrieval of acquired information in MWM and to restore brain serotonergic and dopaminergic turnover dysregulated by D-Gal. These findings confirm the usefulness of oral D-Gal in eliciting rat model of mild memory impairment and show that long-term administration of PCA can be beneficial in reversing detrimental changes related to cognitive deficiencies.

The present study has examined the influence of the prenatal and early life administration of paracetamol on the level of neurotransmitters in the spinal cord of rat pups. The effect of the drug was evaluated in 2-month old Wistar male rats exposed to paracetamol in doses of 5 (P5, n=9) or 15 mg/kg (P15, n=9) p.o. during the prenatal period and after birth until the completion of the second month of life. A parallel control group received tap water (Con, n=9). In this study we have determined the level of monoamines, their metabolites and amino acids in the spinal cord of rats using high performance liquid chromatography (HPLC) in the second month of life. The present experiment demonstrates the action of paracetamol at the molecular level associated with significant modulation of neurotransmission in the spinal cord related to dopaminergic and noradrenergic systems. Simultaneously, paracetamol administration increases the content of an aspartic and glutamic acids in the spinal cord at a critical time during development.

Ring-shaped specimen is commonly used in tests for determination of mechanical properties for arteries in hoop direction, especially for small mammals such as rats or mice. Although ring test is a lot more convenient than the tests concerning strip specimens, interpretation of the experimental data might be inconclusive – it is difficult distinguish whether it's still straightening up or the actual tension begins. The basic problem is to properly define initial length of specimen, which is essential for strain calculation. The purpose of this study was to evaluate various methods for strain evaluation. Ten Wistar Albino Glaxo male rats (3 months old, body weight about 200g) were sacrificed by decapitation and arteries were immediately removed. Three specimens, each approximately 2–3mm long, from each rat were excised adjacent to the aortic arch. Couple different initial lengths, as well as Digital Image Correlation based extensometer results were used for strain-stress response calculations. In addition a 3D Finite Element model, with an Ogden constitutive model based material, was made for deeper investigation of specimen behavior. This study has shown that the testing procedure for determination of mechanical properties of arteries, based on ring-shaped specimen, is prone to errors. Stiffness calculations are very sensitive to the choice of initial length of the specimen. As the use of DIC proved to give very good correlation with experimental data this method will be used in further studies.

Protocatechuic acid has very promising properties potentially useful in the inhibition of neurodegenerative diseases progression. It is the main metabolite of the complex polyphenolic compounds and is believed to be responsible for beneficial effects associated with consumption of the food products rich in polyphenols. Protocatechuic acid is present in the circulation significantly longer and at higher concentrations than parent compounds and easily crosses the blood brain barrier. The aim of the following paper is to provide an extensive and actual report on protocatechuic acid and its pharmacological potential in prevention and/or treatment of neurodegenerative diseases in humans based on existing data from both

Ethnopharmacological relevance Everyday use of the herbal tea rooibos, produced from Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is customary in South Africa, a continuation of its historical use by indigenous people. Although evidence of its traditional indications is anecdotal, rooibos tea is regarded as a general health tea. Aims of the study Available contemporary research indicates to broad cell protective activity of rooibos focusing on its antioxidative, anti-inflammatory, anti-hyperglycaemic and antithrombotic features affecting metabolic syndrome, cardiovascular risk and neuroprotection. Nevertheless little is known about its impact on brain functions. The present experiment aimed to evaluate the possible behavioural and neurochemical effects of long-term oral administration of “fermented”” rooibos herbal tea (FRHT) infusions to adult male Sprague-Dawley rats. Materials and methods Infusions, prepared using 1, 2 and 4 g of “fermented”” (oxidised) A. linearis leaves for 100 ml of hot water, were characterised in terms of flavonoid content by ultra-high and high performance liquid chromatography (UHPLC-qTOF-MS, HPLC-DAD) and administered to rats as sole drinking fluid for 12 weeks. Spatial memory behaviour was assessed in a modified version of the Morris water maze. Dopamine, noradrenaline, serotonin and their metabolite levels (DOPAC, 3-MT, HVA, MHPG, 5-HIAA) were quantified in prefrontal cortex, hippocampus and striatum by HPLC-ECD. Body weight and blood glucose level were additionally estimated. Results All FRHT-treated rats showed improvement of long-term spatial memory defined as increased number of crossings over the previous platform position in SE quadrant of the water maze. It was not accompanied by excessive motor activity. Striatal dopamine and its metabolite 3-MT (3-methoxytyramine) levels were increased in treated rats. There were no differences in body weight gain between control and treated animals but blood glucose level was significantly lower in the latter ones. Conclusion The improvement of long-term memory in FRHT-treated rats and stimulating impact of FRHT on their dopaminergic striatal transmission support the wellness enhancing effect of rooibos tea, contributing to a better understanding of the neurological background of traditional habitual consumption of this herbal tea.

The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum.Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC).The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels.The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS).

Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John WileySons, Ltd.

Animal brain contains a significant amount of zinc, which is a cofactor for more than 300 enzymes. Moreover, it provides the basis for functioning of more than 2000 transcription factors, and it is necessary for memory formation and learning processes in the brain. The aim of this study was to investigate the effect of zinc supplementation on behavior in 3-month-old rats. For this purpose, the Morris water maze paradigm, hole-board, and T-maze were used. Wistar rats received a solution of ZnSO4 in drinking water at the doses of 16 mg/kg (Zn16 group) and 32 mg/kg (Zn32 group). In rats pretreated with the lower dose of zinc, the improvement of the mean escape latency was observed in comparison to the control group and Zn32 group. During memory task, both ZnSO4-supplemented groups showed an increase in crossings over the previous platform position. Furthermore, the exploratory activity in Zn16 group was improved in comparison to Zn32 and control group. In the brains of zinc-supplemented rats, we observed the higher content of zinc, both in the hippocampus and the prefrontal cortex. Hippocampal zinc level correlated positively with the mean annulus crossings of the Zn16 group during the probe trial. These findings show that the long-term administration of ZnS04 can improve learning, spatial memory, and exploratory activity in rats. Graphical Abstract Improvement of spatial learning, memory, and exploratory behavior.

The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established.