Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters.

Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. H. diminuta infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.

Effect of protocatechuic acid on cognitive processes and central nervous system neuromodulators in the hippocampus, prefrontal cortex, and striatum of healthy rats.

OBJECTIVE: : 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. METHODS: : PCA was administered p.o. for 48 days at doses of 50 or 100 mg/kg body weight. The cognitive performance was analysed in behavioural tests (open field, novel object recognition, water maze). Then the animals were sacrificed and their hippocampi, prefrontal cortices and striata removed to measure the level of serotonin, dopamine (DA), noradrenaline, their metabolites and amino acids (taurine, histidine, serine, glutamic acid, aspartic acid, γ-aminobutyric acid, alanine) using high-performance liquid chromatography. RESULTS: : 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. CONCLUSION: : 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.

Early exposure to paracetamol reduces level of testicular testosterone and changes gonadal expression of genes relevant for steroidogenesis in rats offspring.

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.

Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and Affects Neurotransmission in Rats.

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 Prevents Some of the Memory-Related Behavioural and Neurotransmitter Changes in a Pyrithiamine-Induced Thiamine Deficiency Model of Wernicke-Korsakoff Syndrome in Rats.

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.

Long-term Administration of 3-Di-O-Tolylguanidine Modulates Spatial Learning and Memory in Rats and Causes Transition in the Concentration of Neurotransmitters in the Hippocampus, Prefrontal Cortex and Striatum.

The sigma-1 and sigma-2 (σ1 and σ2) receptors are found in high concentrations in the brain, and their altered expression leads to a variety of neuropsychiatric disorders. 3-di-tolylguanidine (DTG) stimulates the activity of both of these receptors. We assessed the effects of administering DTG to adult male Sprague Dawley rats on learning and memory consolidation processes and on the levels of neurotransmitters in selected brain structures. Spatial learning and memory were evaluated in the water maze test. The DTG was administered orally at daily doses of 3 mg/kg (DTG3), 10 mg/kg (DTG10) or 30 mg/kg (DTG30) for 10 weeks before and during the water-maze test. After completion of the experiment, the concentration of monoamines and their metabolites as well as amino acids in structures involved in cognitive performance - the hippocampus, prefrontal cortex, and striatum - were determined using high performance liquid chromatography (HPLC). The DTG10 group showed an improvement in memory processes related to the "new" platform location, whereas the DTG30 group was worse at finding the "old" platform location. Since the administration of DTG led to differences in dopaminergic transmission, it was assumed to influence memory processes in this way. Changes in histidine, serine, alanine, taurine, and glutamic acid levels in selected structures of the brains of rats with memory impairment were also observed. We conclude that long-term administration of DTG modulates spatial learning and memory in rats and changes the concentrations of neurotransmitters in the hippocampus, prefrontal cortex, and striatum..

Effect of intranasal manganese administration on neurotransmission and spatial learning in rats.

The effect of intranasal manganese chloride (MnCl(2)·4H(2)O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2weeks MnCl(2)·4H(2)O at two doses the following: 0.2mg/kg b.w. (Mn0.2) or 0.8mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions.

Aspalathus linearis infusion affects hole-board test behaviour and amino acid concentration in the brain.

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.

Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats.

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.

New hippocampal neurons are not obligatory for memory formation; cyclin D2 knockout mice with no adult brain neurogenesis show learning.

The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs known for their side effects and the results obtained vary greatly. We used a novel approach, cyclin D2 knockout mice (D2 KO mice), specifically lacking adult brain neurogenesis to verify its importance in learning and memory. D2 KO mice and their wild-type siblings were tested in several behavioral paradigms, including those in which the role of adult neurogenesis has been postulated. D2 KO mice showed no impairment in sensorimotor tests, with only sensory impairment in an olfaction-dependent task. However, D2 KO mice showed proper procedural learning as well as learning in context (including remote memory), cue, and trace fear conditioning, Morris water maze, novel object recognition test, and in a multifunctional behavioral system-IntelliCages. D2 KO mice also demonstrated correct reversal learning. Our results suggest that adult brain neurogenesis is not obligatory in learning, including the kinds of learning where the role of adult neurogenesis has previously been strongly suggested.

Pharmacological and biochemical effects of Ginkgo biloba extract on learning, memory consolidation and motor activity in old rats.

Effect of administration of the standardized extract of Ginkgo biloba leaves (EGb 761) on learning, memory and exploratory behavior was estimated in water maze and hole-board tests. Rats (18-month old) received for three months EGb 761 at doses: 50, 100 and 150 mg/kg b.w. per day. After completion of the behavioral experiment, concentrations of neurotransmitters were estimated in selected brain regions. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the control. The increased level of 5-hydroxytryptamine (5-HT) in the hippocampus and 5-HIAA (5-HT metabolite) in the prefrontal cortex correlated positively with the retention of spatial memory. Positive correlation between platform crossings in SE during the probe trial and neurotransmitter turnover suggest improvement of spatial memory. Long-term administration of Ginkgo biloba extract can improve spatial memory and motivation with significant changes in the content and metabolism of monoamines in several brain regions.

Administration of protocatechuic acid affects memory and restores hippocampal and cortical serotonin turnover in rat model of oral D-galactose-induced memory impairment.

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.

Long-term administration of Aspalathus linearis infusion affects spatial memory of adult Sprague-Dawley male rats as well as increases their striatal dopamine content.

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.

Hypothalamus - Response to early paracetamol exposure in male rats offspring.

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 < 0.005). Simultaneously the level of dopamine (DA) (F(2,27) = 4.33, p < 0.05) and its metabolite - homovanillic acid (HVA) (F(2,27) = 17.03, p < 0.005) was increased in the hypothalamus of animals treated with lower dose of the drug. Biochemical analyses show an increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) concentration in P5 group compared to the control rats and group treated with higher dose of paracetamol (F(2,27) = 7.37, p < 0.005). In the hypothalamus significant decrease of glutamic acid concentration was also observed in the group treated with paracetamol at dose of 5 mg. 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.

Early paracetamol exposure decreases brain-derived neurotrophic factor (BDNF) in striatum and affects social behaviour and exploration in rats.

The biochemical and behavioral responses to prenatal and early postnatal exposure to paracetamol in rats are not well understood. The effect of daily maternal and early life administration of 5 mg/kg (group P5) or 15 mg/kg paracetamol (group P15) was evaluated in two-month old male rats, relative to control animals receiving tap water (Con). Social behavior and episodic memory were investigated with Social Interaction and Novel Object Recognition (NOR) tests. Quantification of brain-derived neurotrophic factor (BDNF) was determined in prefrontal cortex, hippocampus and striatum using enzyme-linked immunosorbent assay (ELISA). Control animals exhibited a higher total frequency of social interactions and greater frequency of sniffing compared to rats exposed to paracetamol, and we found a statistically significant increase in the occurrence of pinning in paracetamol-treated animals. Rats from the 15 mg/kg group exhibited a greater interest in objects in the NOR test and spent more time exploring objects during the familiarization and choice phases. Biochemical analysis showed significant differences in striatal BDNF between the groups, specifically, a nearly two-fold decrease in striatal BDNF in the paracetamol groups (P5: 6.78 ±â€¯0.60 pg/mg; P15: 6.06 ±â€¯0.46 pg/mg) relative to the control group (Con: 11.33 ±â€¯2.00 pg/mg). These results indicate that paracetamol exposure induces changes in social behaviour and exploration in rats and results in a significant decrease of striatal BDNF.

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats.

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.

Paracetamol - Effect of early exposure on neurotransmission, spatial memory and motor performance in rats.

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).

Effect of kindled seizures on rat behavior in water Morris maze test and amino acid concentrations in brain structures.

The effects of kindled seizures elicited by repeated pentetetrazole (PTZ) injections, on learning and memory in the Morris water maze test and on concentration of brain amino acids, were examined in rats. It was found that kindled seizures (a model of temporal lobe epilepsy) produced a profound decrease in learning and memory accompanied by a selective and long-lasting decrease in hippocampal and striatal concentration of glutamate, glycine and alanine in the striatum (ex vivo measurement). The concentrations of histamine, serine and gamma-aminobutyric acid (GABA) were not selectively affected by kindling. Alower concentration of glutamate and N-methyl-D-aspartate (NMDA) receptor co-agonists in the striatum (glycine and alanine) indicates the general malfunction of the brain glutamatergic system. It is suggested that a selective decrease in hippocampal glutamate concentration may account for deterioration in learning and memory processes in kindled rats, considering the important role of this neurotransmitter in the cognitive processes (e.g. in the long-term potentiation), and the key contribution of the hippocampus to the spatial memory. The intrinsic mechanisms of the reported behavioral effects may involve neuronal damage in the brain limbic structures, secondary to seizure-induced ischemia and hypoxia.

Influence of Long-Term Zinc Administration on Spatial Learning and Exploratory Activity in Rats.

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.

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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).