[The role of paracetamol in transition reactions of alpha-nitrogen and oxidative stress in the liver]. / Rola paracetamolu w reakcjach przemian azotu alfa-aminowego oraz stresu oksydacyjnego w watrobie.

Paracetamol (Acetaminophen, PC) is metabolized in liver to N-acetyl-p-benzoquinon-imine (NAPQI), that is in turn conjugated by glutathione S-transferase with glutathione. NAPQI inhibits the respiratory chain. It may cause a 90% decrease of ATP concentration in mitochondria of hepatocytes. The oxidation of paracetamol to quinine form can also generate free radicals. Both above mentioned processes, can injure the mitochondria and cells. There have not been found in accessible literature any data dealing with paracetamol influence on the process elimination of the alpha nitrogen in the liver. The ATP concentration decline may lead to disturbances in mitochondrial enzymes. There are discrepant data of the role of free radicals in the mechanism of toxic action of paracetamol.

Nitric oxide modulates the amphetamine effect on [3H]glucose uptake in the brain of rats prenatally exposed to lead.

Glucose is the main source of energy for the central nervous system (CNS). In this study, we examined the effects of the psychostimulant amphetamine (AMPH) and the neuronal mediator nitric oxide (NO) on [3H]glucose uptake in the brain of adult rats that had been prenatally exposed to lead. Lead [Pb(CH3COO)2 . 3H2O; 250 ppm] was added to the drinking water of pregnant Wistar rats for the duration of pregnancy. On the day of parturition, lead was discontinued as an additive in the drinking water. Offspring remained ith dams for 21 days. The control group consisted of rats that consumed water without lead. In adulthood, male offspring from both groups (lead-exposed and control) were pretreated with 7-nitroindazole (nNOS blocking agent) (10.0 mg/kg ip) or saline (1.0 ml/kg ip), 30 min before AMPH (1.0 mg/kg ip). After another 30 min, and 15 min before termination, all rats were injected with 6-[3H]-D-glucose (500 muCi/kg ip). Brain specimens were taken (striatum, frontal cortex, hippocampus, and thalamus with hypothalamus, and pons with medulla oblongata) for determination of radioactivity in a liquid scintillation counter. We found that lead did not alter [3H]glucose uptake in brain regions studied (with exception of frontal cortex) but that AMPH increased [3H]glucose uptake in the striatum, frontal cortex and hippocampus, and that the AMPH effect was lessened in the hippocampus of lead-exposed rats. Moreover, the AMPH effect on [3H]glucose uptake in the frontal cortex, hippocampus, thalamus with hypothalamus and pons of control rats was potentiated by 7-NI pretreatment. Similar effect was observed in lead-intoxicated rats (striatum, frontal cortex and hippocampus). These results indicate that NO modulates AMPH-induced [3H]glucose uptake in the brain of rats prenatally exposed to lead.

Trimetazidine increases [3H]glucose uptake in rat brain.

Trimetazidine, a clinically effective antianginal agent with no negative inotropic or vascular properties, acts by optimizing cardiac energy metabolism through inhibition of free fatty acid oxidation, shifting substrate utilization from fatty acids to glucose. Up to now there has been no study associating trimetazidine's effect on metabolic processes with glucose utilization in the mammalian brain. The objective of the present study was to determine if trimetazidine altered [(3)H]glucose uptake in rat brain. Adult male Wistar rats were administered trimetazidine (Metazydyna, Polfa) either as a single dose (10.0 mg/kg po) or for 14 consecutive days (5.0 mg/kg po per day) or vehicle saline (2.0 ml/kg po). Sixty minutes after the single dose or 14th dose of trimetazidine, and 15 min before experiment termination and brain dissection, 6-[(3)H]D-glucose (500 Ci/kg ip; Amersham) was administered. Using liquid scintillation counting, trimetazidine, either in a single or multiple dose regimen, was found to increase [(3)H]glucose uptake (DPM/100 mg of wet tissue) in all dissected regions of the brain (i.e., striatum, hippocampus, frontal cortex, thalamus with hypothalamus, pons with medulla oblongata, and cerebellum). Therefore, central effects need to be taken into consideration as possibly adding to known beneficial cardiac effects of trimetazidine.

[Influence of prenatal exposition for selenium on visual evoked potentials (FVEP) in rats]. / Wzrokowe potencjaly wywolane (FVEP) kory mózgowej u szczurów po prenatalnej ekspozycji na selen.

Selenium is an essential trace element in lower concentration and toxic in higher one. The aim of the study was to find out if the small doses of selenium taken by pregnant rats change the visual evoked potential (FVEP) curve in newborns. The FVEP was done in 4-6 month old white, Wistar, offsprings rats. 8 rats were from the mothers which drank water solution of natrium selenosum in dose 1.5 ppm through the whole pregnant time ( selen group) and 8 rats were from the pure farm (control group). The shortened of the latencies and increased of the amplitudes of N1 and P1 waves were observed in the selenium exposed group in comparison to the control, but only the changes between amplitudes of N1 and P1 were statistically significant. The small doses of selenium by improving the VEP may probably change for the better vision too.

[Visual evoked potentials (FVEP) after the prenatal exposure to heavy metals--experimentals studies]. / Wzrokowe potencjaly wywolane (FVEP) po prenatalnym stosowaniu soli metali ciezkich--badania doswiadczalne.

PURPOSE: To find out, if any and how deep alterations in visual tract are due to prenatal intoxication by heavy metals such as: cadmium (Cd), lead (Pb), mercury (Hg) and manganese (Mn). The measure of these alterations were the changes in flash visual evoked potentials after prenatal intoxication. MATERIAL AND METHODS: The experiments were carried out on 55 white newborns Wistar rats, which were divided into 5 groups: control group (14 rats), Cd group (12), Pb (6), Hg (14) and Mn (9). The method of the FVEP study was described by Pojda et al. RESULTS: The latencies of the peaks N1 and P1 were prolonged in the Mn group till 113-118% (p< 0.05). Slight prolongation of N1 latencies about 1% in Cd and Hg groups and of 4% in Pb group were not statistically significant. The differences of P1 latencies were not statistically significant in these groups, compared to the control group. The amplitude of N1 wave decreased in Cd group about 63% and in Mn group of 32% compared to the control (p<0.05). In Hg intoxicated group the N1 amplitude decreased to 56% (p< 0.01). The amplitude of P1 decreased in all intoxicated groups (Hg of 56%, Cd 55%, Mn 49%) statistically significant, except the Pb one, in which even 21% decrease was not significant. CONCLUSIONS: The heavy metals prolonged the latencies and diminished the amplitudes of flash visual evoked potentials, so may be, they are not only neurotoxic but also "ophthalmotoxic" factors.

Impairment in Pain Perception in Adult Rats Lesioned as Neonates with 5.7-Dihydroxytryptamine.

BACKGROUND: Whereas some studies have demonstrated the essential role of 5-hydroxytryptamine (5-HT) in tramadol and acetaminophen analgesia, other research has presented conflicting results. To dispel doubts, some aspects of the involvement of 5-HT in the antinociceptive properties of these drugs remain to be clarified. OBJECTIVES: The aim of this study was to determine whether the serotoninergic system dysfunction produced by neonatal 5-HT lesion in rats may affect the antinociceptive effects of tramadol and acetaminophen administered in adulthood. MATERIAL AND METHODS: Three days after birth, the control rats were pretreated with desipramine HCl (20 mg/kg i.p.) 30 min before intraventricular saline--vehicle injection. A separate group received 5.7-DHT; 2×35 µg in each lateral ventricle. At the age of 8 weeks, 5-HT and 5-hydroxyidoleaceticacid (5-HIAA) concentrations were determined in the thalamus and spinal cord by an HPLC/ED method. The antinociceptive effects of tramadol (20 mg/kg i.p.) or acetaminophen (100 mg/kg i.p.) were evaluated by a battery of tests. RESULTS: 5.7-DHT lesioning was associated with a reduction in 5-HT and 5-HIAA content of the thalamus (>85% and >90%) and spinal cord (>58% and 70%). Neonatal 5.7-DHT treatment produced a significant reduction in the antinociceptive effect of tramadol in the hot plate, tail-immersion, paw withdrawal and writhing tests. In the formalin hind paw test, the results were ambiguous. 5-HT lesion was also associated with a decrease in the analgesic effect of acetaminophen in the hot plate and writhing tests. A similar relationship wasn't found in the other assessments conducted with the use of acetaminophen. CONCLUSIONS: The present study provides evidence that (1) an intact serotoninergic system is required for the adequate antinociceptive action of tramadol, and (2) the serotoninergic system exerts a negligible influence on acetaminophen-induced analgesia in rats. We hypothesize that similar abnormalities in nociception may occur in patients with 5-HT dysfunction (e.g. depression), so these results should be complied in analgesic dosage adjustment.

Perinatal manganese exposure and hydroxyl radical formation in rat brain.

The present study was designed to investigate the role of pre- and postnatal manganese (Mn) exposure on hydroxyl radical (HO(•)) formation in the brains of dopamine (DA) partially denervated rats (Parkinsonian rats). Wistar rats were given tap water containing 10,000 ppm manganese chloride during the duration of pregnancy and until the time of weaning. Control rat dams consumed tap water without added Mn. Three days after birth, rats of both groups were treated with 6-hydroxydopamine at one of three doses (15, 30, or 67 µg, intraventricular on each side), or saline vehicle. We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy. In neonates, the major organs that accumulated Mn were the femoral bone and liver. However, Mn was not elevated in tissues in adulthood. To determine the possible effect on generation of the reactive species, HO(•) in Mn-induced neurotoxicity, we analyzed the contents of 2.3- and 2.5-dihydroxybenzoic acid (spin trap products of salicylate; HO(•) being an index of in vivo HO(•) generation), as well as antioxidant enzyme activities of superoxide dismutase (SOD) isoenzymes and glutathione S-transferase (GST). 6-OHDA-depletion of DA produced enhanced HO(•) formation in the brain tissue of newborn and adulthood rats that had been exposed to Mn, and the latter effect did not depend on the extent of DA denervation. Additionally, the extraneuronal, microdialysate, content of HO(•) in neostriatum was likewise elevated in 6-OHDA-lesioned rats. Interestingly, there was no difference in extraneuronal HO(•) formation in the neostriatum of Mn-exposed versus control rats. In summary, findings in this study indicate that Mn crosses the placenta but in contrast to other heavy metals, Mn is not deposited long term in tissues. Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in HO(•) generation, and the effects of Mn and 6-OHDA are compounded. Moreover, HO(•) generation parallels the suppression of SOD isoenzymes and GST in the brains of rats lesioned with 6-OHDA and/or intoxicated with Mn-the most prominent impairments being in frontal cortex, striatum, and brain stem. In conclusion, ontogenetic Mn exposure, resulting in reactive oxygen species, HO(•) formation, represents a risk factor for dopaminergic neurotoxicity and development of neurodegenerative disorders.

Serotoninergics attenuate hyperlocomotor activity in rats. Potential new therapeutic strategy for hyperactivity.

Hyperactivity is thought to be associated with an alteration of dopamine (DA) neurochemistry in brain. This conventional view became solidified on the basis of observed hyperactivity in DA-lesioned animals and effectiveness of the dopaminomimetics such amphetamine (AMP) in abating hyperactivity in humans and in animal models of hyperactivity. However, because AMP releases serotonin (5-HT) as well as DA, we investigated the potential role of 5-HT in an animal model of hyperactivity. We found that a greater intensity of hyperactivity was produced in rats when both DA and 5-HT neurons were damaged at appropriate times in ontogeny. Therefore, previously we proposed this as an animal model of attention deficit hyperactivity disorder (ADHD) - induced by destruction of dopaminergic neurons with 6-hydroxydopamine (6-OHDA) (neonatally) and serotoninergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) (in adulthood). In this model effects similar to that of AMP (attenuation of hyperlocomotion) were produced by m-chlorophenylpiperazine (m-CPP) but not by 1-phenylbiguanide (1-PG), respective 5-HT2 and 5-HT3 agonists. The effect of m-CPP was shown to be replicated by desipramine, and was largely attenuated by the 5-HT2 antagonist mianserin. These findings implicate 5-HT neurochemistry as potentially important therapeutic targets for treating human hyperactivity and possibly childhood ADHD.

[Selenium plasma concentrations in children with celiac disease in different stages of diagnosis]. / Stezenie selenu w surowicy u dzieci z celiakia na róznych etapach diagnostyki tego schorzenia.

Selenium is an important nutritional factor of human diet. Epidemiological and experimental data indicate that low selenium level can be associated with increased risk of cancer. On the other hand there are some evidence that patients with celiac disease can present selenium deficiency and increased risk of certain malignancies. Therefore the aim of study was to evaluate plasma selenium levels in children with celiac disease. The level of selenium was estimated by flame atomic absorptiometry method according to Whiteside. Celiac disease was diagnosed according to ESPGHAN criteria. Obtained results indicate that in celiac disease low plasma selenium levels are especially marked at preliminary stage of diagnosis and following low compliance to the gluten free diet. Children with this sickness may need supplementation of their diet with selenium.

Ontogenetic manganese exposure with perinatal 6-OHDA lesioning alters behavioral responses of rats to dopamine D1 and D2 agonist treatments.

The effect of neonatal manganese (Mn) exposure in a 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease was investigated. Pregnant Wistar rats were given drinking water with 10,000 ppm of Manganese (MnCl2.4H2O) from the time of conception until weaning on the 21st day after delivery. Control rats consumed tap water. Three days after the birth, other groups of neonatal rat pups were pretreated with desipramine (20 mg/kg ip 1h) prior to bilateral ICV administration of 6-OHDA or its vehicle, saline-ascorbic (0.1%) (control). Two months after the birth, striatal dopamine and homovanilic acid efflux measured by an in vivo microdialysis method were reduced in rats lesioned with 6-OHDA. Co-exposure to perinatal Mn did not modify neurotransmission alterations. However, there were prominent abnormalities in behavioral testing in rats perinatally exposed to Mn and treated neonatally with 6-OHDA. These findings demonstrate that although Mn did not further damage neurotransmitter activity in the neostriatum, ontogenetic exposure to Mn enhances the behavioral toxicity to 6-OHDA.

Neonatal DSP-4 treatment modifies antinociceptive effects of the CB1 receptor agonist methanandamide in adult rats.

To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB(1)-receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc × 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB(1) receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex (>90 %) and spinal cord (>80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB(1) receptor density in the brain.

Thioperamide, an H3 receptor antagonist prevents [³H]glucose uptake in brain of adult rats lesioned as neonates with 5,7-dihydroxytryptamine.

As a first attempt at exploring an association between histaminergic and serotoninergic neuronal phenotypes in glucose regulation, the influence of the histamine H3 receptor antagonist thioperamide on glucose uptake by brain was determined in rats in which the serotoninergic innervations of brain was largely destroyed perinatally. Male Wistar rats were initially treated on the 3rd day after birth with the serotoninergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) (75 µg icv) or saline vehicle (10 µl icv). At 8 weeks lesioned and control rats were terminated in order to validate the effectiveness of 5,7-DHT: reduction in 5-HT and 5-HIAA by 83-91% and 69-83% in striatum, frontal cortex, and hippocampus (HPLC/ED method). Other groups of rats were pretreated with thioperamide (5.0 mg/kg ip) or saline vehicle 60 min prior to 6-[³H]-D-glucose (500 µCi/kg ip). Fifteen-min later rats were decapitated and brains were excised and dissected to remove frontal cortex, striatum, hippocampus, thalamus/hypothalamus, pons, and cerebellum. Liquid scintillation spectroscopy was used to determine that [³H]glucose uptake, which was enhanced in 5,7-DHT lesioned rats in cortex (by 88%), hippocampus, thalamus/hypothalamus, pons and cerebellum (each by 47-56%), and in striatum (by 35%). In contrast, thioperamide prevented the enhancement in [³H]glucose uptake in all brain regions of 5,7-DHT neonatally lesioned rats; and [³H]glucose levels were significantly different in all brain regions (except thalamus/hypothalamus) in thioperamide-versus saline-treated rats. These findings indicate a functional association between histaminergic and serotoninergic systems in brain in relation to glucose regulation.

Ontogenetic exposure of rats to pre- and post-natal manganese enhances behavioral impairments produced by perinatal 6-hydroxydopamine.

Rats lesioned shortly after birth with 6-hydroxydopamine (6-OHDA; 134 µg icv) represent a near-ideal model of severe Parkinson's disease because of the near-total destruction of nigrostriatal dopaminergic fibers. The element manganese, an essential cofactor for many enzymatic reactions, itself in toxic amount, replicates some clinical features similar to those of Parkinson's disease. The aim of this study was to examine the effect of neonatal manganese exposure on 6-OHDA modeling of Parkinson's disease in rats. Manganese (MnCl(2)·4H(2)O) 10,000 ppm was included in the drinking water of pregnant Wistar rats from the time of conception until the 21st day after delivery, the age when neonatal rats were weaned. Control rats consumed tap water. Other groups of neonatal rat pups, on the 3rd day after birth, were pretreated with desipramine (20 mg/kg ip 1 h) prior to bilateral icv administration of 6-OHDA (30, 60, or 137 µg) or its vehicle saline-ascorbic (0.1%) (control). At 2 months after birth, in rats lesioned with 30, 60, or 134 µg 6-OHDA, endogenous striatal dopamine (DA) content was reduced, respectively, by 66, 92, and 98% (HPLC/ED), while co-exposure of these groups to perinatal manganese did not magnify the DA depletion. However, there was prominent enhancement of DA D(1) agonist (i.e., SKF 38393)-induced oral activity in the group of rats exposed perinatally to manganese and also treated neonatally with the 30 mg/kg dose of 6-OHDA. The 30 mg/kg 6-OHDA group, demonstrating cataleptogenic responses to SCH 23390 (0.5 mg/kg) and haloperidol (0.5 mg/kg ip), developed resistance if co-exposed to perinatal manganese. In the group exposed to manganese and lesioned with the 60 mg/kg dose of 6-OHDA, there was a reduction in D(2) agonist (i.e., quinpirole, 0.1 mg/kg)-induced yawning. The series of findings demonstrate that ontogenetic exposure to manganese results in an enhancement of behavioral toxicity to a moderate dose of 6-OHDA, despite the fact that there is no enhanced depletion of striatal DA depletion by the manganese treatment.

Ontogenetic serotoninergic lesioning alters histaminergic activity in rats in adulthood.

The aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats lesioned as neonates with the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At 3 days after birth Wistar rats were pretreated with desipramine (20 mg/kg ip) before bilateral icv administration of 5,7-DHT (37.5 µg base on each side) or saline-ascorbic (0.1%) vehicle (control). At 10 week levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were determined in frontal cortex, striatum, and hippocampus by an HPLC/ED technique. In the hypothalamus, frontal cortex, hippocampus and medulla oblongata, the level of histamine was analyzed by an immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped activity) were performed, and effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists S(+)chlorpheniramine (H(1)), cimetidine (H(2)), and thioperamide (H(3)) were determined. We confirmed that 5,7-DHT profoundly reduced contents of 5-HT and 5-HIAA in the brain in adulthood. Histamine content was also reduced in all examined brain regions. Moreover, in 5,7-DHT-lesioned rats the locomotor and oral activity responses to thioperamide were altered, and apomorphine-induced stereotype was intensified. From the above, we conclude that an intact central serotoninergic system modulates histamine H(3) receptor antagonist effects on the dopaminergic neurons in rats.

Effect of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors on the concentration of insulin-like growth factor-1 (IGF-1) in hypercholesterolemic patients.

UNLABELLED: Studies have shown that HMG-CoA reductase inhibitors (statins) play an important role in the prevention and treatment of atherosclerosis and hyperlipidemia. The aim of this study was to investigate the effect of 3-month treatment with simvastatin on serum levels of Insulin-Like Growth Factor-1 (IGF-1) in patients with diagnosed hypercholesterolemia. In total, 156 patients with hypercholesterolemia were recruited for the study. The inclusion criteria for this study were designed to allow the enrollment of a representative group of patients for cytokine studies. The patients were divided into two groups: (1) patients with a mild-to-moderate risk of heart disease, who had total cholesterol (TC) < 300 mg/dl (7.8 mmol/l), LDL-cholesterol < 210 mg/dl (5.4 mmol/l), and who lacked risk factors for coronary artery disease (CAD) after treatment with a diet for 3 months; (2) patients with a high-to-very high risk of CAD, who had TC > 300 mg/dl (7.8 mmol/l), LDL-cholesterol > 210 mg/dl (5.4 mmol/l), and at least two risk factors for CAD after treatment with a diet and administration of simvastatin (20 mg/day) for a three month period. The control group consisted of ten healthy volunteers who each had a normal lipid profile. Total cholesterol, LDL-cholesterol and IGF-1 concentrations were measured at baseline and either after six months of dietary supplementation (first group) or after three months of dietary supplementation and three months of simvastatin treatment (second group). CONCLUSIONS: In patients with mild-to-moderate risk of CAD, a decreased serum concentration of IGF-1 was observed three months after beginning a low-fat diet. However, no changes in the serum concentration of IGF-1 were noted in patients with high-to-very high risk of CAD. Additional three-month treatment with simvastatin decreased the serum concentration of IGF-1.

Histaminergic activity in a rodent model of Parkinson's disease.

Rats lesioned shortly after birth with 6-OHDA have been proposed to be a near-ideal model of severe Parkinson's disease, because of non-lethality of the procedure, near-total destruction of nigrostriatal dopaminergic fibers, and near-total dopamine (DA) denervation of striatum. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. Therefore, the aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats. At 3 days after birth, Wistar rats were pretreated with desipramine (20.0 mg/kg ip) 1 h before bilateral icv administration of the catecholaminergic neurotoxin 6-OHDA (67 microg base, on each side) or saline-ascorbic acid (0.1%) vehicle (control). At 8 weeks levels of DA and its metabolites L: -3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) were estimated in the striatum and frontal cortex by HPCL/ED technique. In the hypothalamus, hippocampus, frontal cortex, and medulla oblongata, the level of histamine was analyzed by immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped-activity) were additionally made on control and 6-OHDA neonatally lesioned rats. Effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists (e.g., S(+)chlorpheniramine, H(1); cimetidine, H(2); thioperamide, H(3) agonist) were determined. We confirmed that 6-OHDA significantly reduced contents of DA and its metabolites in the brain in adulthood. Histamine content was significantly increased in the hypothalamus, hipocampus, and medulla oblongata. Moreover, in 6-OHDA-lesioned rats behavioral response was altered mainly by thioperamide (H(3) antagonist). These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that histaminergic neurons exert a modulating role in Parkinsonian 6-OHDA-lesioned rats.

Influence of dopamine on flash visual evoked potentials (FVEP) in prenatally mercury intoxicated rats.

The female adult white Wistar rats were given tap water (control) or 50 ppm of methylmercury chloride (MMC) ad libitum throughout their pregnancies. Newborn rats drank mother's milk during the first 21 days after delivery and then only tap water. The study was carried out on three-month old offsprings of white Wistar rats. The flash visual evoked potentials (FVEP) were recorded before and after injecting of 10 microl 0.9% saline, 50 or 100 nmols of dopamine (DA) into the lateral brain ventricle by method used before in our laboratory. The amplitude of the first deep negative (N(1)) peak significantly increased to 109-114% after both doses of DA in the control group and to 138-139% in mercury-treated animals. The amplitude of the next positive (P(1)) wave decreased to 94% and 86% in the control group after 50 and 100 nmols of DA, respectively. In Hg-treated group after 50 nmols of DA, the value dropped down to 91%, but increased to 109% after 100 nmols of DA. The increasing of DeltaN(1)P(1) was observed in the control group to 112% after 50 nmols and to 109% after 100 nmols of DA and in Hg-exposed rats, respectively, to 127% and to 129%. The described changes were statistically significant (p < 0.05). The N(1) and P(1) latencies were prolonged in the control group after both doses of DA. In Hg-treated group, the prolongation of N(1) latency was recorded, while the P(1) latency was not changed. We concluded that prenatal Hg intoxication disturbed the effect of DA on FVEP.