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Central benzodiazepine receptor occupancy by zolpidem in the human brain as assessed by positron emission tomography.

The central benzodiazepine receptor occupancy by zolpidem in man is unknown. The present study used positron emission tomography (PET) and [11C]flumazenil to assess in five healthy volunteers, central benzodiazepine receptor occupancy in brain regions with high receptor densities 1 h following an acute oral administration of twice the usual hypnotic dose of zolpidem (20 mg). Receptor occupancy was measured in five discrete structures (middle frontal gyrus, middle temporal gyrus, posterior occipital cortex, lateral parietal cortex, and cerebellar cortex) and in a large neocortical area as the fractional change in the [11C]flumazenil bound/free ratio for the interval 15-40 min post-administration of the radiotracer. The free-radioligand concentration was estimated from the pons, a reference structure virtually devoid of central benzodiazepine receptor. With individual pons values, mean occupancy was about 21% but with spurious inter-subject variability. With pons values averaged across the five subjects and separately for control and treated condition, the occupancy was (mean +/- S.D.) 27 +/- 11% for the whole neocortex, and ranged from 26 to 29% in the five discrete structures (P < 0.01). By showing hypnotic effect at moderate occupancies, this study directly provides evidence for the full-agonist properties of zolpidem in human.

Adult↗

Recovery of stress-induced increases in noradrenaline turnover is delayed in specific brain regions of old rats.

Male Wistar rats at 2 and 12 months of age were sacrificed before, immediately following, and at 6 and 24 hours after a 3-hour immobilization stress period. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in eight brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases of MHPG-SO4 levels in all brain regions examined and significant elevations in plasma corticosterone levels in both 2 and 12 month old rats. In 2 month old rats, the MHPG-SO4 levels in all brain regions returned to control levels within 6 hours after release from the stress. However, in 12 month old rats, the metabolite levels in the hypothalamus, amygdala, pons plus medulla oblongata (pons+med. obl .) and midbrain still remained at significantly increased levels at 6 and 24 hours after the stress. Moreover, in the amygdala of older rats, stress-induced decreases in NA levels persisted even 6 hours after stress. Plasma corticosterone levels also showed significant elevations at 6 and 24 hours after the stress only in 12 month old rats. These results suggest that brain NA metabolism during recovery periods from an acute exposure to a stressful situation is altered by the aging process in such a manner that NA neurons in the hypothalamus, amygdala, pons+med. obl . and midbrain in older rats remain activated by stressful stimuli for prolonged periods of time following release from stress.

Aging↗

Down-regulation of central receptors for thyrotropin-releasing hormone in kappa opiate agonist-induced abstinence in the rat.

The effect of U-50,488H, a selective kappa opiate agonist, on tolerance-dependence and abstinence on the TRH receptors of the spinal cord and discrete regions of the brain of male Sprague-Dawley rats was determined. Rats were injected intraperitoneally twice daily with 25 mg/kg of U-50,488H for 4 days. Rats serving as controls were injected with the vehicle. On day 5, rats which were labeled as tolerant to U-50,488H were injected with U-50,488H (25 mg/kg) and sacrificed 1 hr later, whereas those labeled as abstinent were sacrificed without any injection. The above procedure has been previously shown to produce a high degree of tolerance to the analgesic and hypothermic effects of U-50,488H. The spinal cord and regions of the brain (hippocampus, cortex, midbrain, hypothalamus, corpus striatum, pons and medulla, and amygdala) were isolated for binding studies. The ligand [3H]MeTRH was used for TRH receptors. The binding constants, Bmax and Kd values, of [3H]MeTRH to bind to membranes prepared from various regions of the brain and spinal cord of rats tolerant-dependent on U-50,488H were unaffected. However, in rats abstinent to U-50,488H, the binding of [3H]MeTRH to membranes of the hypothalamus, and pons and medulla, was decreased. The decreased binding of [3H]MeTRH to hypothalamic membranes was due to changes in Bmax value, while in pons and medulla it was due to an increase in the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Sex differences in the effects of inescapable footshock on central catecholaminergic and serotonergic activity.

In two experiments sex differences in changes in central noradrenergic, dopaminergic and serotonergic activity were measured immediately after a 30-min session of inescapable footshocks. In Experiment 1 concentrations of noradrenaline, dopamine, serotonin and their major metabolites were determined in the frontal cortex, hypothalamus, amygdala, striatum, mesencephalon and the medulla-pons area. Inescapable shock increased the activity of all 3 transmitter systems, as evidence by increased metabolite concentrations in specific brain areas. Shock-induced increments in metabolite levels were larger in females than in males, especially for the serotonergic system. In addition, shock presentation resulted in a decrement in the noradrenaline content in most areas studied. In the frontal cortex, noradrenaline was reduced by inescapable shock in males but not in females. In Experiment 2, sex-dependent neurochemical consequences of predictable versus unpredictable shocks were studied in the frontal cortex and the medulla-pons area. Similar to Experiment 1, both brain parts showed large shock-induced increments in the activity of the catecholaminergic systems. Differential effects of predictable and unpredictable shock were not found (frontal cortex) or were rather small (medulla-pons) and appeared sex-dependent for serotonin in this area. The sex differences in neurochemical change found in the first experiment were largely replicated in the second experiment. The relevance of the observed sex differences in central neurotransmitter reactivity for sex differences in behavior is discussed.

3,4-Dihydroxyphenylacetic Acid↗

Changes in brain amines associated with cancer anorexia.

Analysis of indole amine metabolism within acute (Walker 256 carcinosarcoma) and chronic (methycholanthrene-induced sarcoma) animal models of cancer anorexia demonstrated elevated levels of plasma free tryptophan, whole brain tryptophan, serotonin and 5-hydroxyindoleacetic acid in anorectic tumor-bearing rats. Whole brain levels of catecholamines were not changed within either tumor line. Regional central nervous system determination of tryptophan metabolism in rats bearing Walker 256 tumors revealed elevated tryptophan in the hypothalamus, corpus striatum, mesencephalon, diencephalon, cerebellum and cortex, increased serotonin in the diencephalon and cerebellum and elevated 5-hydroxyindoleacetic acid in the diencephalon, hippocampus, pons-medulla, cerebellum and cortex. Although tryptophan was significantly increased only in the corpus striatum and diencephalon of the more chronic methycholanthrene tumor model, serotonin concentration was elevated in the corpus striatum, diencephalon, hippocampus, pons-medulla, cerebellum and cortex, while levels of 5-hydroxyindoleacetic acid were significantly increased in all these areas as well as in the mesencephalon. Since similar changes in indole activity were not observed in pair-fed control rats, it is concluded that the elevated serotonin and 5-hydroxyindoleacetic acid levels in tumor-bearing rats did not result from undernutrition alone. Assay of regional catecholamines revealed few food-relevant changes, with norepinephrine being elevated in the corpus striatum and decreased in the pons-medulla of tumor-bearing rats. Therefore, these experiments suggest that the increased serotonin metabolism observed in tumor-bearing rats may be involved in the etiology of the anorexia of cancer.

Amino Acids↗

Origin and distribution of brain-stem somatosensory evoked potentials in humans.

The distribution of somatosensory evoked potentials (SEPs) recorded from the brain-stem surface was studied to investigate their generator sources in 14 patients during surgical exploration of the posterior fossa. Two distinct SEPs of different morphologies and electrical orientation were obtained by median nerve stimulation. A small positive-large negative-late prolonged positive wave was recorded from the cuneate nucleus and its vicinity. There was a phase-reversal between the cuneate nucleus and the ventral surface of the medulla, depicting a dipole for dorso-ventral organization. From the pons and midbrain, triphasic waves with predominant negativity were obtained. This type of SEP had identical wave forms between the dorsal, lateral and ventral surface of the pons and midbrain. It showed an increase in negative peak latency as the recording sites moved rostrally, suggesting an ascending axial orientation. In a patient with pontine hemorrhage, the killed end potential, a large monophasic positive potential was obtained from the lesion. This potential occurs when an impulse approaches but never passes beyond the recording electrode. Therefore, the triphasic SEP from the pons and midbrain reflects an axonal potential generated in the medial lemniscal pathway.

Adolescent↗

Contribution of brain injury to hypertension following intravenously-administered pancuronium in rats.

Abnormal hypertension sometimes occurs following intravenous administration (i.v.) of pancuronium in patients with brain injury. The present experiment was designed to determine whether brain injury contributes to the hypertensive response of i.v. pancuronium. Forty-six Wister strain rats were studied, of which 39 had induced brain injury at (a) upper pons (b) midbrain (c) thalamus region (excluding hypothalamus) and (d) cerebellum or a combination of these sites. The injury was made by single insertion of a 22 Gauge needle through the skull surface. The quantity of pancuronium solution administered i.v. in each case was 1.0 ml containing either 0.8 mg/kg or 8 mg/kg of pancuronium. Group A (n = 7) had no brain injury and the mean arterial pressure (MAP) did not change following i.v. administration of pancuronium. In Group B (n = 9) (a+b+c, 8.0 mg/kg) MAP rose from 90.9 +/- 15.4 to 102 +/- 22.0 mmHg and in Group C (n = 7) (a+b+c, 0.8 mg/kg) MAP rose from 148.4 +/- 13.3 to 160 +/- 14.4 mmHg. In Group D (n = 5) (b+c, 8.0 mg/kg) MAP remained unchanged. In Group E (n = 5) (a, 8.0 mg/kg) MAP rose from 130.3 +/- 18.7 to 146 +/- 27.6 mmHg and in Group F (n = 6) (a, 0.8 mg/kg) MAP rose from 129.7 +/- 15.6 to 135.8 +/- 13.8 mmHg. In Group G (n = 7) (d, 8.0 mg/kg) MAP remained unchanged. Since the MAP was elevated in only those groups that received injury in the upper pons, we concluded that injury in the upper pons can lead to hypertension following i.v. administration of pancuronium.

Animals↗

Decreases of action potential amplitudes, in sodium-free and calcium-free conditions, of identifiable giant neurons of an African giant snail (Achatina fulica Férussac)--I. The right parietal ganglion.

Decreases of the action potential amplitude in sodium- and calcium-free states were observed with respect to the four giant neurons, PON (periodically oscillating neuron), Tan (tonically autoactive neuron), RAPN (right anterior pallial neuron) and d-RPLN (dorsal-right parietal large neuron), identified in the right parietal ganglion of the suboesophageal ganglia of an African giant snail (Achatina fulica Férussac). The decrease of the PON action potential amplitude, caused in the sodium-free state, was observed to be 25.4 +/- 2.1% (23.0 +/- 2.0 mV), expressed by M +/- SE, while that of the calcium-free state was 35.0 +/- 2.1% (30.9 +/- 1.7 mV). Then, the two ionic dependencies of the PON action potential were estimated to be about 40-50% on sodium and 50-60% on calcium. The decrease of the TAN action potential in the sodium-free state, was observed to be 20.7 +/- 1.2% (18.8 +/- 1.3 mV), whereas that of the calcium-free state was 42.2 +/- 2.7% (39.0 +/- 2.2 mV), indicating that the two ionic dependencies were 30-40% on sodium and 60-70% on calcium. The decrease of the RAPN action potential in the sodium-free state, was 45.8 +/- 3.7% (40.3 +/- 3.1 mV), whereas that of the calcium-free state was 21.7 +/- 2.5% (17.8 +/- 2.0 mV), indicating that the two ionic dependencies were about 70% on sodium and about 30% on calcium. The decrease of the d-RPLN action potential in the sodium-free state was found to be 17.6 +/- 2.4% (15.2 +/- 1.8 mV), whereas that of the calcium-free state was 23.1 +/- 1.4% (20.8 +/- 1.4 mV), indicating that the two ionic dependencies were 40-50% on sodium and 50-60% on calcium. The action potential amplitudes of all the neurons tested were decreased in both sodium-free and calcium-free states. However, their ionic dependencies were estimated to vary from 70% on sodium (30% on calcium) to 30% on the sodium (70% on the calcium), according to the neurons tested.

Action Potentials↗

Acute action of luteinizing hormone on mouse Leydig cells: accumulation of mitochondrial phosphoproteins and stimulation of testosterone synthesis.

Upon stimulation of Leydig cells with luteinizing hormone (LH) or dibutyryl-3',5'-cyclic AMP (Bt2cAMP) at 37 degrees C, two mitochondrial phosphoproteins accumulate with the same stimulant dose response as the increased rate of testosterone synthesis. The proteins pp32 and pp30 have apparent isoelectric points of 6.6 and 6.5 and molecular weights of approximately 32 30 kDa respectively, as determined by two-dimensional polyacrylamide gel electrophoresis. These two phosphoproteins are not detected in mouse adipose or liver cells nor in the total testicular cell population, of which Leydig cells constitute a small percentage. However, both proteins are also observed in mouse adrenal cells stimulated by ACTH or Bt2cAMP. The appearance of pp32 and pp30 is prevented by inhibitors of cytosolic protein translation, indicating that only newly synthesized protein is available as a substrate for phosphorylation. Proteolytic peptide mapping indicates that both of these mouse Leydig and adrenal proteins have structural similarity to pp30 (formerly denoted as ib), the 30 kDa mitochondrial phosphoprotein that we have observed previously in peptide hormone or Bt2cAMP-stimulated rat adrenal cortex (Pon, L.A., Hartigan, J.A. and Orme-Johnson, N.R. (1986) J. Biol. Chem. 261, 13309-13316; Alberta, J.A., Epstein, L.F., Pon, L.A. and Orme-Johnson, N.R. (1989) J. Biol. Chem. 264, 2368-2372) and rat corpus luteum cells (Pon, L.A. and Orme-Johnson, N.R. (1986) J. Biol. Chem. 261, 6694-6599). Since pp32 is a larger mitochondrial protein of similar primary structure to pp30, it is a potential precursor of this protein. Finally, the detection of the mitochondrial phosphoprotein pp30 in a third steroidogenic tissue type and a third species provides further correlative evidence that the production of pp30 may be an integral part of the subcellular mechanism by which peptide hormones stimulate steroid hormone biosynthesis.

Adipose Tissue↗

Castration affects brain iodomelatonin binding in hamsters maintained in long but not short days.

The effects of castration on 2-[125I]iodomelatonin ([125I]melatonin) binding sites in discrete brain areas were investigated in male Syrian hamsters exposed to long and short days. In hamsters maintained in long days (14 h light: 10 h darkness), castration produced a marked decrease in [125I]melatonin binding in the brain, particularly in the medulla-pons hypothalamus and hippocampus. Maximal response in the medulla-pons and hypothalamus was observed at 3 days; specific [125I]melatonin binding subsequently increased to reach control levels within 30 days after castration. In the hippocampus, the decrease in [125I]melatonin binding was still evident at 90 days after castration and could be reversed by testosterone. Exposure to short days (8 h light: 16 h darkness) did not affect [125I]melatonin binding in the various brain areas of the intact hamsters; even after 90 days when circulating testosterone decreased to castrated levels, the binding remained as in intact, long-day-housed controls. Moreover, [125I]melatonin binding in the various brain areas of hamsters exposed to short days was unaffected by castration. The results clearly indicate that the regulation by testosterone of melatonin receptors in the medulla-pons, hypothalamus and hippocampus of the male hamster depends on the prevailing photoperiod.

Animals↗

Differential binding of [3H]MK-801 to brain regions and spinal cord of mice treated chronically with morphine.

1. The effects of morphine tolerance and abstinence on the binding of [3H]MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors were determined in brain regions and spinal cord of the mouse. 2. Male Swiss-Webster mice were rendered tolerant to and physically dependent on morphine by subcutaneous implantation of a pellet containing 75 mg of morphine base for 3 days. Placebo pellet-implanted mice served as controls. In tolerant (nonabstinent) mice, the pellets were left intact at the time of sacrificing whereas, in the abstinent mice, the pellets were removed 6 hr prior to sacrificing. 3. The binding of [3H]MK-801 to membranes prepared from spinal cord and brain regions (cortex, pons-medulla, hypothalamus, hippocampus, amygdala, striatum, and midbrain) was determined by using a 5 nM concentration of the ligand in the presence of 30 microM glycine and 50 microM of glutamate. 4. In nonabstinent morphine-tolerant mice, the binding of [3H]MK-801 was decreased in pons-medulla and hypothalamus, but was increased in the spinal cord in comparison to that in placebo controls. The reduction in binding in pons-medulla was due to a decrease in the Bmax value; the Kd value remained unchanged. The binding of [3H]MK-801 was increased in the hippocampus of morphine-abstinent mice. 5. These studies demonstrate that NMDA receptors of brain regions and spinal cord are differentially affected in morphine-tolerant and abstinent mice.

Animals↗

Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat.

The effect of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenergic neurons in the rat has been investigated using neurochemical techniques. The results demonstrated a preferential effect of DSP4 on the locus coeruleus noradrenergic neuron system without any notable effects on the dopamine and adrenaline neurons and only a minor neurotoxic effect on the serotonin neurons. The effect of DSP4 on the serotonin neurons could be completely prevented by pretreatment with the uptake blocker zimelidine, without affecting the action of DSP4 on noradrenergic neurons. Neonatal DSP4 treatment systemically led to permanent depletions of noradrenaline in the cerebral cortex and spinal cord and marked increases of noradrenaline in the cerebellum and pons-medulla. These effects of DSP4 were dose-dependent and could be blocked by pretreatment with the noradrenaline uptake blocker desipramine. The alterations in endogenous noradrenaline levels were quantitatively similar to changes observed in [3H]noradrenaline uptake in slices in vitro. There were no significant changes of these noradrenergic parameters when analysing the whole CNS after neonatal DSP4 treatment, in spite of marked regional changes in both directions. Administration of DSP4 to rats of different ages produced acutely marked depletions of noradrenaline in all regions including the pons-medulla and the cerebellum at all developmental stages. Marked and permanent depletions of noradrenaline were found in the distant noradrenergic nerve terminal projections after treatment at all ages, whereas increases in noradrenaline levels in the pons-medulla and cerebellum were only observed in rats treated with DSP4 up to the age of 3-5 days, whereas a DSP4 administration in older rats led to substantial and permanent depletions of noradrenaline in both these regions. The results indicate that the alteration of the postnatal development of noradrenergic neurons after treatment of rats up to the age of 3-5 days is mainly related to a 'pruning effect' of DSP4, in which prevention of the development of distant nerve terminal projections causes an increased outgrowth of nerves in collateral systems spared by the neurotoxin. The results indicate that DSP4 may be a useful denervation tool for studying various aspects of noradrenergic neurotransmission of developing locus coeruleus neurons.

Amines↗

Proopiomelanocortin peptide immunocytochemistry in rhesus monkey brain.

The immunocytochemical distribution of proopiomelanocortin (POMC) peptides (beta-endorphin, ACTH, alpha-MSH, 16K fragment) was studied in the brain of the rhesus monkey (Macaca mulatta). Some animals were administered colchicine intracerebroventricularly prior to sacrifice to enhance the visualization of perikaryal immunoreactivity. Immunoreactive perikarya are localized to hypothalamic infundibular nucleus, giving rise to several distinct projections. Rostral projections extend through midline diencephalic and preoptic areas, and enter the telencephalon. Along this course, immunoreactive fibers are seen in midline hypothalamic and preoptic nuclei, nucleus of the diagonal band, olfactory tubercle, nucleus accumbens, bed nucleus of stria terminalis, septum, and other limbic structures in telencephalon. Caudal to the anterior commissure, some fibers ascend dorsally to enter the midline thalamus, which they innervate. Lateral projections of the infundibular perikarya course through the medial-basal hypothalamus, dorsal to the optic tracts, and enter the amygdala region where they innervate more medially situated amygdaloid nuclei. Caudal projections of the POMC neurons also extend through midline diencephalon, some coursing along a periventricular path to innervate midline hypothalamic and thalamic nuclei. This projection extends into the mesencephalic substantia grisea centralis and may also contribute to the innervation of more dorsally situated nuclei in the pons and medulla, such as the parabrachial nuclei and nucleus tractus solitarius. Other caudal projections originating in the hypothalamus course through the ventral tegmentum of mesencephalon and pons and may contribute to the innervation of midline raphe and other ventrally situated nuclei in the pons and medulla. The distribution of immunoreactive perikarya and fibers in the brain of rhesus monkey is strikingly similar to that found in the rat brain. However, subtle differences appear to exist in the innervation patterns of particular brain regions.

Adrenocorticotropic Hormone↗

Distribution of catecholamines in the central nervous system of the pig.

The objective of this study was to document, through comprehensive means, normal distribution and concentration of catecholamines in various regions of the CNS of pigs, an increasingly popular animal model used for transgenic manipulation of neural genes. The effects of gonadal steroidal status on this distribution were also assessed by comparing CNS catecholamine concentrations among mature male pigs (boars), immature (gilts) and mature female pigs (sows), and adult male pigs castrated prepuberally (barrows). Dissected tissue samples from the CNS were extracted in 2 N acetic acid, filtered through a 0.2 micron filter, then quantitated by reverse-phase high performance liquid chromatography using a C-18 reverse phase column with electrochemical detection. In both boars and sows the highest concentrations of norepinephrine (NE) were found in the diencephalic areas and brain stem. Gilts exhibited elevated concentrations of NE in the olfactory bulbs (OB), hypothalamus, pons, and corpus trapezoideum-locus ceruleus (LC) compared to lower concentrations in corresponding areas of sows. Prepuberal castration of the male was associated with significantly lower NE concentrations in the striatum, periaqueductal area (PAG), pons, LC, and spinal cord. The sow exhibited significantly lower NE concentrations in the mammillary area (Mam), PAG, pons, and spinal cord than those in corresponding areas of the boar. Dopamine concentrations appeared to be similar in all areas of the brain and spinal cord studied in the sow and boar. Results demonstrated that prepuberal castration of the male appears to significantly alter the DA content of the Mam and dorsal spinal cord, in contrast to gilts who possess significantly higher concentrations of DA. It is concluded from our studies that in general, catecholamine concentrations in various regions of the brain and spinal cord of sexually mature pigs parallel distributions of neuropeptides, substance P, and methionine enkephalin, as previously reported. In addition, significant association was found between gonadal activity and catecholamine concentrations in discrete areas of the pig brain.

Animals↗

Projections of tachykinin- and glutaminase-containing rat retinal ganglion cells.

Glutamate (Glu) and the tachykinin substance P (SP) have been proposed as neurotransmitters or neuromodulators of the retinal projection to the brain. In the present study, we demonstrate that tachykinin-like (TK) immunoreactivity (IR) accumulates in rat retinal axons following electrical lesions to the optic tract, indicating that SP is conveyed in the optic nerve to its central targets. In addition, we show that eye enucleation causes a dramatic decrease in TK-IR fibers in the pretectal olivary nucleus (PON), but not in other retinorecipient nuclei of the thalamus and the midbrain, and that Fluorogold injected into the pretectum is retrogradely transported to the somata of TK-IR retinal ganglion cells (RGCs), indicating an important projection of TK-IR RGCs to the PON. We also show that most rat RGCs are labeled with antibodies against phosphate-activated glutaminase, an enzyme considered to generate the transmitter pool of glutamate. Unlike TK-IR fibers, phosphate-activated glutaminase-IR structures disappear in most retinorecipient nuclei following eye enucleation. The present results give neuroanatomical support to the idea that glutamate is a neurotransmitter in the retinal projection and suggest an important role for TK-IR RGCs in the relay of visual information to the PON.

Animals↗

Developing rat brain monoamine levels following in utero exposure to a mixture of 2,4-dichlorophenoxyacetic and 2,4,5-trichlorophenoxyacetic acids.

Pregnant rats were gavaged with a 1:1 mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) at 0 (G0), 50 (G 50) and 100 (G 100) mg/kg per day on gestational days 6-15. Treatment significantly (P less than 0.05) delayed ontogeny of dopamine (DA), but not norepinephrine (NE) levels, in the thalamus-hypothalamus on postnatal day 7; in the pons-medulla on days 7,9 and 15; and in the olfactory lobes on day 9. On day 25, serotonin (5-HT) levels were significantly decreased in the pons-medulla of G 100 rats, whereas 5-hydroxyindoleacetic acid (5-HIAA) levels decreased in the thalamus-hypothalamus and pons-medulla of G 50 and G 100 rats.

2,4,5-Trichlorophenoxyacetic Acid↗

Alterations in the metabolism of serotonin and dopamine in the mouse brain following a single administration of allylnitrile, which induces long-term dyskinesia.

The effects of allylnitrile (ALN), which induces a long-term dyskinesia in mice, on the metabolism of serotonin (5-HT) and dopamine (DA) were studied after a single administration. One day after injection, ALN produced a significant increase in the levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA): 5-HT in the brain cortex, medulla oblongata plus pons, hypothalamus and midbrain; 5-HIAA in the cortex, medulla oblongata plus pons, striatum, hypothalamus and midbrain; the ratio of 5-HIAA/5-HT in the medulla oblongata plus pons, striatum and midbrain; HVA in the cortex and midbrain. These changes were not seen 10 and 35 days after injection when the animals were showing behavioral abnormalities. The present findings suggest that changes in 5-HT and DA metabolism are involved in the appearance of the dyskinetic syndrome.

Administration, Oral↗

Vitamin C preserves the cardio-protective paraoxonase activity of high-density lipoprotein during oxidant stress.

HDL-associated paraoxonase (PON) antioxidant enzyme activity is cardio-protective. We investigated whether vitamin C prevented loss of PON activity from HDL during oxidant stress. HDL was incubated with either hydrophilic or lipophilic peroxyl radical initiators in the absence (control) or presence of vitamin C (50 and 100 micromol/L). Regardless of the type of radical, accumulation of lipid oxidation products in HDL was similar in incubations lacking vitamin C. Loss of PON activity was greater in HDL exposed to hydrophilic, in contrast to lipophilic, radicals, but addition of vitamin C maintained enzyme activity. Vitamin C's capacity to attenuate loss of the HDL ability to prevent atherogenic modification of LDL (assessed as electrophoretic mobility) was, however, modest, and appeared limited only to those incubations in which HDL was exposed to lipophilic radicals. Our results indicate that vitamin C may, under some conditions, prevent loss of cardio-protective function from HDL during oxidant stress.

Aryldialkylphosphatase↗