Antidepressive Effects of Taraxacum Officinale in a Mouse Model of Depression Are Due to Inhibition of Corticosterone Levels and Modulation of Mitogen-Activated Protein Kinase Phosphatase-1 (Mkp-1) and Brain-Derived Neurotrophic Factor (Bdnf) Expression.

BACKGROUND Depression is a common disorder linked with high levels of chronicity, psycho-social and physical problems, and suicide. Here, we assessed the antidepressant effects of the hydromethanolic extract of Taraxacum officinale and investigated the underlying mechanism. MATERIAL AND METHODS Antidepressant effects were examined by use of the tail suspension test (TST). Concentrations of corticosterone, dopamine, noradrenaline, and adrenaline were examined by biochemical assays. The mRNA expression was assessed by quantitative RT-PCR. Phytochemical analysis was performed by LC/MS. RESULTS The results showed that the extract at the dosage of 50 and 100 mg/kg significantly (p<0.01) alleviated the TST-induced immobility in the mice, and the effects were comparable to the antidepressant drug Bupropion, which was used as the positive control. Investigation of the underlying mechanism revealed that the T. officinale extract exerts it effects by significantly (p<0.05) decreasing the levels of corticosterone and increasing the concentrations of dopamine, noradrenaline, and adrenaline. Further, the extract also increased the expression of brain-derived neurotrophic factor (Bdnf), which was associated with significant (p<0.05) decrease in the expression of mitogen-activated protein kinase phosphatase-1 (Mkp-1), indicative of the antidepressant potential of T. officinale. Finally, the active constituents of the extract, which include isoetin, hesperidin, naringenin, Kaempferol, sinapinic, and gallic acid, were also identified, which could potentially be responsible for its antidepressant effects. CONCLUSIONS In conclusion, T. officinale exerts significant antidepressant effects in a mouse model of depression by inhibition of corticosterone levels and modulation of Mkp-1 and Bdnf expression.

Simultaneous determination of epinephrene and paracetamol at copper-cobalt oxide spinel decorated nanocrystalline zeolite modified electrodes.

In this study, CuCo2O4 and CuCo2O4 decorated nanocrystalline ZSM-5 materials were prepared. For comparative study, a series of MCo2O4 spinels were also prepared. Materials were characterized by the complementary combination of X-ray diffraction, N2-adsorption, UV-visible, and electron microscopic techniques. A simple and rapid method for the simultaneous determination of paracetamol and epinephrine at MCo2O4 spinels modified electrodes is presented in this manuscript. Among the materials investigated in this study, CuCo2O4 decorated nanocrystalline ZSM-5 exhibited the highest electrocatalytic activity with excellent stability, sensitivity, and selectivity. Analytical performance of the sensor was demonstrated in the determination of epinephrine and paracetamol in the commercial pharmaceutical samples.

Hindbrain medulla catecholamine cell group involvement in lactate-sensitive hypoglycemia-associated patterns of hypothalamic norepinephrine and epinephrine activity.

Cell-type compartmentation of glucose metabolism in the brain involves trafficking of the oxidizable glycolytic end product, l-lactate, by astrocytes to fuel neuronal mitochondrial aerobic respiration. Lactate availability within the hindbrain medulla is a monitored function that regulates systemic glucostasis as insulin-induced hypoglycemia (IIH) is exacerbated by lactate repletion of that brain region. A2 noradrenergic neurons are a plausible source of lactoprivic input to the neural gluco-regulatory circuit as caudal fourth ventricular (CV4) lactate infusion normalizes IIH-associated activation, e.g. phosphorylation of the high-sensitivity energy sensor, adenosine 5'-monophosphate-activated protein kinase (AMPK), in these cells. Here, we investigated the hypothesis that A2 neurons are unique among medullary catecholamine cells in directly screening lactate-derived energy. Adult male rats were injected with insulin or vehicle following initiation of continuous l-lactate infusion into the CV4. Two hours after injections, A1, C1, A2, and C2 neurons were collected by laser-microdissection for Western blot analysis of AMPKα1/2 and phosphoAMPKα1/2 proteins. Results show that AMPK is expressed in each cell group, but only a subset, e.g. A1, C1, and A2 neurons, exhibit increased sensor activity in response to IIH. Moreover, hindbrain lactate repletion reversed hypoglycemic augmentation of pAMPKα1/2 content in A2 and C1 but not A1 cells, and normalized hypothalamic norepinephrine and epinephrine content in a site-specific manner. The present evidence for discriminative reactivity of AMPK-expressing medullary catecholamine neurons to the screened energy substrate lactate implies that that lactoprivation is selectively signaled to the hypothalamus by A2 noradrenergic and C1 adrenergic cells.

An electronic tongue: evaluation of the masking efficacy of sweetening and/or flavoring agents on the bitter taste of epinephrine.

An epinephrine (E) tablet is under development for sublingual (SL) administration for the first-aid treatment of anaphylaxis; however, the inherent bitterness of E may hinder acceptability by patients, especially children. To assess the degree of E bitterness and to predict the masking effects of sweetening and/or flavoring non-medicinal ingredients (NMIs), the potential usefulness of an electronic tongue (e-Tongue) was evaluated. The e-Tongue sensors were conditioned, calibrated, and tested for taste discrimination. Six standard active pharmaceutical ingredients were used to build and validate a bitterness model which was then used to assess E bitartrate (EB) solutions from 0.3-9 mM. Taste-masking efficiency of aspartame (ASP), acesulfame potassium (ASK), and citric acid (CA) each at 0.5 mM was evaluated. Using EB 9 mM, the bitterness score was 20 on a scale of 20 (unacceptable) down to 1 (not detected). When NMIs 0.5 mM were added, neither ASK (17.2, unacceptable) nor was ASP (14.0, limit acceptable) effective in masking the bitter taste. When the combination of ASK and ASP was used, the bitterness score was reduced to 9.2 (acceptable). However, the addition of CA alone resulted in the best reduction of the bitterness score to 3.3 (not detected). Using the e-Tongue, the incorporation of a variety of sweetening and/or flavoring NMIs into a SL tablet of E could be shown to mask its bitter taste by up to 80%. These results should be confirmed by in vivo studies.

Brain insulin infusion does not augment the counterregulatory response to hypoglycemia or glucoprivation.

Although high dosages of insulin can cause hypoglycemia, several studies suggest that increased insulin action in the head may paradoxically protect against severe hypoglycemia by augmenting the sympathoadrenal response to hypoglycemia. We hypothesized that a direct infusion of insulin into the third ventricle and/or the mediobasal hypothalamus (MBH) would amplify the sympathoadrenal response to hypoglycemia. Nine-week-old male rats had insulin (15 mU) or artificial cerebrospinal fluid (aCSF, control) infused bilaterally into the MBH or directly into the third ventricle. During the final 2 hours of the brain insulin or aCSF infusions, the counterregulatory response to either a hyperinsulinemic hypoglycemic (approximately 50 mg/dL) clamp or a 600-mg/kg intravenous bolus of 2-deoxyglucose (2DG) was measured. 2-Deoxyglucose was used to induce a glucoprivic response without peripheral insulin infusion. In response to insulin-induced hypoglycemia, epinephrine rose more than 60-fold, norepinephrine rose more than 4-fold, glucagon rose 8-fold, and corticosterone rose almost 2-fold; but these increments were not different in aCSF vs insulin treatment groups with either intracerebroventricular or bilateral MBH insulin protocols. Intracerebroventricular insulin infusion stimulated insulin signaling as noted by a 5-fold increase in AKT phosphorylation. In the absence of systemic insulin infusion, 2DG-induced glucopenia resulted in an equal counterregulatory response with brain aCSF and insulin infusions. Under the conditions studied, although insulin infusion acted to stimulate hypothalamic insulin signaling, neither intrahypothalamic nor intracerebroventricular insulin infusion augmented the counterregulatory response to hypoglycemia or to 2DG-induced glucoprivation. Therefore, it is proposed that the previously noted acute actions of insulin to augment the sympathoadrenal response to hypoglycemia are likely mediated via mechanisms exterior to the central nervous system.

Capillary electrophoretic separation of biologically active amines and acids using nanoparticle-coated capillaries.

This manuscript describes dynamic coating of capillaries with poly(L-lysine) (PLL) and silica nanoparticles (SiO2 NPs) and use of the as-prepared capillaries for the separation of biogenic amines and acids by CE in conjunction with LIF detection. The directions of EOF are controlled by varying the outmost layer of the capillaries with PLL and SiO2 NPs, respectively. Over the pH range 3.0-5.0, the (PLL-SiO2NP)n-PLL capillaries have an EOF toward the anodic end and are more suitable for the separation of acids with respect to speed, while the (PLL-SiO2NP)n capillaries have an EOF toward the cathodic end and are more suitable for the separation of biogenic amines regarding speed and sensitivity. The separations of standard solutions containing five amines and two acids by CE with LIF detection using (PLL-SiO2NP)2-PLL and (PLL-SiO2NP)3 capillaries were accomplished within 10 and 7 min, providing plate numbers of 3.8 and 5.0x10(4) plates/m for 5-hydroxytryptamine (5-HT), respectively. The LODs for 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) are 32 and 2 nM and 0.2 and 1.5 nM when using the (PLL-SiO2NP)2-PLL and (PLL-SiO2NP)3 capillaries, respectively. Identification and quantification of 5-HIAA, homovanillic acid, and DL-vanillomandelic acid in urine samples from a male before and after drinking green tea were tested to validate practicality of the present approach. The results show that the (PLL-SiO2NP)2-PLL capillary provides greater resolving power, while the (PLL-SiO2NP)3 capillary provides better sensitivity, higher efficiency, and longer durability for the separation of the amines and acids.

Separation and determination of epinephrine and dopamine in traditional Chinese medicines by micellar electrokinetic capillary chromatography with laser induced fluorescence detection.

A micellar electrokinetic capillary chromatography method with laser-induced fluorescence detection was developed for the analysis of epinephrine and dopamine after derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole. The optimum derivatization conditions were: 30 mM sodium borate (pH adjusted to 8.0 with 1.0 M HCl), reaction time 30 min at 60 degrees C. Baseline separation was achieved within 14 min with a running buffer composed of 10 mM sodium borate + 25 mM sodium dodecyl sulfate (pH adjusted to 9.5 with 0.1 M NaOH) and an applied voltage of 15 kV. Good linearity relationships (correlation coefficients: 0.9991 for epinephrine and 0.9985 for dopamine) between peak areas and concentrations of the analytes were obtained. The detection limits and quantification limits for epinephrine and dopamine were 0.0038 mg/L and 0.013 mg/L, and 0.065 mg/L and 0.020 mg/L, respectively. The method was applied to the analysis of the two compounds in two Chinese medicines with recoveries in the range of 92.6-108.7%.

Fast-disintegrating sublingual tablets: effect of epinephrine load on tablet characteristics.

The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9:1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content uniformity, hardness, disintegration time, wetting time, and friability were measured for each formulation at each compression force. All 4 tablet formulations at each compression force were within the United States Pharmacopeia (USP) limits for weight variation and content uniformity. A linear increase in compression force resulted in an exponential increase in hardness for all formulations, a linear increase in disintegration and wetting times of A, and an exponential increase in disintegration and wetting times of B, C, and D. At a mean +/- SD hardness of > or = 2.3 +/- 0.2 kg, all tablet formulations passed the USP friability test. At a mean +/- SD hardness of < or = 3.1 +/- 0.2 kg, all tablet formulations resulted in disintegration and wetting times of <10 seconds and <30 seconds, respectively. Tablets with drug loads from 0% to 24% epinephrine can be formulated with hardness, disintegration times, and wetting times suitable for sublingual administration.

Noise-stress-induced brain neurotransmitter changes and the effect of Ocimum sanctum (Linn) treatment in albino rats.

In this modern world, stress and pollution are unavoidable phenomena affecting the body system at various levels. A large number of people are exposed to potentially hazardous noise levels in daily modern life, such as noise from work environments, urban traffic, and household appliances. A variety of studies have suggested an association between noise exposure and the occurrence of disorders involving extra-auditory organs such as disorders of the nervous, endocrine, and cardiovascular systems. In this study, Wistar strain albino rats were subjected to 100 dB broadband white noise, 4 h daily for 15 days. The high-pressure liquid chromatographic estimation of norepinephrine, epinephrine, dopamine, and serotonin in discrete regions of the rat brain indicates that noise stress can alter the brain biogenic amines after 15 days of stress exposure. Ocimum sanctum (OS), a medicinal herb that is widely claimed to posses antistressor activity and used extensively in the Indian system of medicine for a variety of disorders, was chosen for this study. Administration of the 70% ethanolic extract of OS had a normalizing action on discrete regions of brain and controlled the alteration in neurotransmitter levels due to noise stress, emphasizing the antistressor potential of this plant.

Growth hormone improves bioenergetics and decreases catecholamines in postinfarct rat hearts.

The aims of this study were to examine, in vivo, the effects of GH treatment on myocardial energy metabolism, function, morphology, and neurohormonal status in rats during the early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague Dawley rats. Three different groups were studied: MI rats treated with saline (n = 7), MI rats treated with GH (MI + GH; n = 11; 3 mg/kg x day), and sham-operated rats (sham; n = 8). All rats were investigated with 31P magnetic resonance spectroscopy and echocardiography at 3 days after MI and 3 weeks later. After 3 weeks treatment with GH, the phosphocreatine/ATP ratio increased significantly, compared with the control group (MI = 1.69 +/- 0.09 vs. MI + GH = 2.42 +/- 0.05, P < 0.001; sham = 2.34 +/- 0.08). Treatment with GH significantly attenuated an increase in left ventricular end systolic volume and end diastolic volume. A decrease in ejection fraction was prevented in GH-treated rats (P < 0.05 vs. MI). Myocardial and plasma noradrenaline levels were significantly lower in MI rats treated with GH. These effects were accompanied by normalization of plasma brain natriuretic peptide levels (sham = 124.1 +/- 8.4; MI = 203.9 +/- 34.7; MI + GH = 118.3 +/- 8.4 ng/ml; P < 0.05 vs. MI). In conclusion, GH improves myocardial energy reserve, preserves left ventricular function, and attenuates pathologic postinfarct remodeling in the absence of induction of left ventricular hypertrophy in postinfarct rats. The marked decrease in myocardial content of noradrenaline, after GH treatment, may protect myocardium from adverse effects of catecholamines during postinfarct remodeling.

Increased body fat mass and suppression of circulating leptin levels in response to hypersecretion of epinephrine in phenylethanolamine-N-methyltransferase (PNMT)-overexpressing mice.

Epinephrine is a major stress hormone that plays a central role in the control of metabolic function and energy homeostasis. To evaluate the role of epinephrine and the physiological and pathophysiological consequences of sustained elevation of epinephrine on metabolic and endocrine function, we studied several metabolic parameters and circulating leptin levels in a newly developed transgenic mouse model of phenylethanolamine-N-methyltransferase (PNMT) overexpression. A 100-fold overexpression of PNMT and subsequent elevation of epinephrine levels resulted in a marked suppression of circulating leptin levels in the transgenic animals (1.14 +/- 0.05 vs. 2.17 +/- 0.35 ng/ml; P < 0.01), which correlated negatively with plasma epinephrine (r = -0.82; P < 0.05), thus providing evidence for an inhibitory action of epinephrine on leptin production in vivo. In parallel, we found a marked increase in the body fat content of the transgenic animals (12.54 +/- 1.5 vs. 6.22 +/- 0.2%; P < 0.01) that was accompanied by enlarged adipocytes, indicating an increased lipid storage in PNMT transgenic mice. Interestingly, however, transgenic animals had normal body weight and did not exhibit major alterations in carbohydrate metabolism, as evidenced by analysis of random and fasted blood glucose levels, plasma insulin and C peptide levels, and insulin tolerance test. The metabolic alterations observed were not secondary to changes in food intake or increased activity of the hypothalamic-pituitary-adrenal axis, as there were no differences in these parameters. In summary, sustained primary overproduction of epinephrine resulted in suppression of plasma leptin levels and increased lipid storage in the PNMT transgenic mice. The concerted action of the sympathoadrenal system and reduced leptin may contribute to defending energy reservoirs while maintaining a normal body weight, which may be of vital importance under conditions of stress and energy deficiency.

Evidence of a role for neuropeptide Y and monoamines in mediating the appetite-suppressive effect of GH.

Among the many responses to GH administration is suppression of voluntary feed intake (FI) in some species, attributed to improvement in the efficiency of nutrient utilization and, therefore, reduced need for ingested substrates. Commercial broiler chickens have been genetically selected for generations for rapid growth, realized largely via the major correlated response of increased voluntary feed consumption. Neuropeptide Y (NPY) and monoamines play very important roles in the central regulation of feeding. Preliminary studies from our laboratory suggest that the appetite-suppressive effect of GH may be independent of its actions as a repartitioning agent, and may involve alterations in NPY expression at the pre-translational level. The purpose of this investigation was to explore the dose-response nature of the appetite-suppressive effect of GH in juvenile broilers, and the possible involvement of NPY and monoamines in this process. A GH dose-response study was conducted using 8-week-old female broilers infused i.v. with GH in a pulsatile pattern for 7 days at 0, 10, 50, 100 or 200 microgram/kg body weight per day. Hypothalamic NPY and epinephrine (EP) concentrations decreased in a dose-related manner with GH. At the highest dosage, voluntary FI decreased 19% (P<0.05) and hypothalamic NPY mRNA decreased approximately 50% in the infundibular nuclei and midline region (P<0.0001). In contrast, birds pairfed to the high-GH dosage group did not differ from controls, verifying that changes in NPY and monoamines were not secondary to reduced FI. We conclude that hypothalamic NPY and EP are likely candidates to explore further as mediators of the appetite-suppressive effect of GH.

Location and electrophysiological characterization of rostral medullary adrenergic neurons that contain neuropeptide Y mRNA in rat medulla.

The objective of this study was to characterize the projection pattern and electrophysiological properties of the rostral medullary adrenergic neurons (C(1)) that express neuropeptide Y (NPY) mRNA in rat. NPY mRNA was found in a variable fraction of tyrosine hydroxylase immunoreactive (TH-IR) neurons depending on the medullary level. By retrograde labeling (Fast Blue, FluoroGold), NPY mRNA was detected in virtually all C(1) cells (96%) and C(3) cells (100%) with hypothalamic projections but in only 9% of C(1) cells and 58% of C(3) cells projecting to thoracic segment 3 (T(3)) or T(6) of the spinal cord. To identify the electrophysiological properties of the C(1) cells that express NPY mRNA, we recorded from baroinhibited neurons within the C(1) region of the ventrolateral medulla (RVLM) and tested for projections to segment T(3), the hypothalamus, or both. By using the juxtacellular method, we labeled these cells with biotinamide and determined whether the recorded neurons were TH-IR and contained NPY mRNA. At rostral levels (Bregma -11.8 mm), barosensitive neurons had a wide range of conduction velocities (0.4-6.0 m/second) and discharge rates (2-28 spikes/second). Most projected to T(3) only (27 of 31 cells), and 4 projected to both the hypothalamus and the spinal cord. Most of the baroinhibited cells with spinal projections but with no hypothalamic projections had TH-IR but no NPY mRNA (11 of 17 cells). Only 1 cell had both (1 of 17 cells), and 5 cells had neither (5 of 17 cells). Both TH-IR and NPY mRNA were found in neurons with dual projections (2 of 2 cells). At level Bregma -12.5 mm, baroinhibited neurons had projections to the hypothalamus only (13 of 13 cells) and had unmyelinated axons and a low discharge rate. Four of five neurons contained both TH-IR and NPY mRNA, and 1 neuron contained neither. In short, NPY is expressed mostly by C(1) cells with projection to the hypothalamus. NPY-positive C(1) neurons are barosensitive, have unmyelinated axons, and have a very low rate of discharge. Most bulbospinal C(1) cells with a putative sympathoexcitatory role do not make NPY.

Occlusal disharmonies modulate central catecholaminergic activity in the rat.

Occlusal disharmonies have classically been thought to be involved in the etiopathogenesis of bruxism, as have, more recently, alterations in central neurotransmission, particularly dopaminergic neurotransmission. However, the connection between these two factors has still not been established. In this study, we assessed the effects of diverse occlusal disharmonies, maintained for either 1 day or 14 days, on neurochemical indices of dopaminergic and noradrenergic activity in the striatum, frontal cortex, and hypothalamus of the rat. The in vivo activity of tyrosine hydroxylase, determined as the accumulation of 3,4-dihydroxyphenylalanine (DOPA), 30 min after the administration of 3-hydroxybenzylhydrazine, a DOPA decarboxylase inhibitor, and dopamine and noradrenaline contents were quantified by high-performance liquid chromatography with electrochemical detection. The wearing of an acrylic cap on both lower incisors for 1 day induced a significant increase in DOPA accumulation in the regions analyzed, with parallel increases in dopamine levels in the hypothalamus and dopamine and noradrenaline in the frontal cortex. After the cap was maintained for 14 days, DOPA accumulation tended to return to control values, except in the left striatum, thereby causing an imbalance between hemispheres. In contrast, 1 or 14 days after the lower left and the upper right incisors were cut, less pronounced changes in catecholaminergic neurotransmission were found in the brain areas studied. Moreover, the cutting of one lower incisor did not modify either DOPA accumulation or dopamine and noradrenaline contents in the striatum or hypothalamus. These results provide experimental evidence of a modulation of central catecholaminergic neurotransmission by occlusal disharmonies, being dependent on the nature of the incisal alteration and on the time during which it was maintained.

Effects of the trichothecene mycotoxin T-2 toxin on neurotransmitters and metabolites in discrete areas of the rat brain.

T-2 toxin has been shown to affect the central nervous system. Only recently have attempts been made to characterize the neurochemical perturbations associated with T-2 intoxication. To examine the effect of T-2 on regional brain biogenic monoamines and selected metabolites, male rats were dosed orally with T-2 toxin in corn oil at 0.1, 1.0 or 2.5 mg/kg body weight. At 2, 6 and 10 hr post-dosing, rats were killed, brains were collected and stored at -80 degrees until analysed. Brain nuclei, including nucleus raphe magnus, paraventricular nucleus, locus coeruleus, substantia nigra, medial forebrain bundle, nucleus accumbens and olfactory tubercle, were analysed. T-2 treatment increased 5-hydroxy-3-indoleacetic acid and serotonin throughout the brain, and produced a transient increase in norepinephrine in the nucleus raphe magnus and a temporary decrease in the substantia nigra. Regional dihydroxyphenylacetic acid concentration was affected, with increased DOPAC observed in the locus coeruleus, medial forebrain bundle and paraventricular nucleus of the hypothalamus, and decreased DOPAC in the olfactory tubercles. No regional changes in epinephrine or dopamine were observed. Few treatment differences were observed, with the 0.1 mg/kg body weight T-2, 2% of the LD50, significantly affecting brain monoamines. It had been suggested that neurological manifestations of T-2 toxin are the result of brain hypoxia; however, the altered brain monoamine profile observed at doses that do not alter heart function, suggests the brain is a primary site of trichothecene action.

Central effects of dehydroepiandrosterone in Zucker rats.

OBJECTIVES: To investigate whether dehydroepiandrosterone (DHEA), an adrenal/gonadal androgen, can act centrally to reduce energy intake in a model of genetic obesity, the Zucker fatty rat. To investigate a possible mechanism of action. DESIGN: Two experiments were performed in lean and obese female Zucker rats. In the first experiment, 24 h following administration of i.p. DHEA (200 mg/kg), three hypothalamic regions [lateral hypothalamus (LH), ventromedial nucleus (VMH), and paraventricular nucleus (PVN)] were analyzed for monoamine neurotransmitter concentrations. In the second experiment, DHEA (50 micrograms) was administered by i.c.v. injection. Energy intake for the following day was measured. MEASUREMENTS: In the first experiment, concentrations of norepinephrine (NE), epinephrine (EPI), dopamine (DA), serotonin (5HT), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured. Ratios of 5HT/5HIAA were calculated. In the second experiment, kilojoules consumed per 24 h were calculated. RESULTS: All LH monoamines, and PVN DA, displayed lower concentrations in obese than lean control rats. DHEA treatment reversed these reductions in obese rats without affecting lean rats. DHEA increased VMH EPI in obese rats only. DHEA increased PVN NE in both lean and obese rats. I.C.V. DHEA decreased energy intake in obese but not lean rats. CONCLUSION: The i.c.v. results suggest that DHEA exerts a phenotype specific, centrally mediated inhibitory effect on food intake. In addition, in doses previously shown to reduce energy intake in obese but not lean rats, i.p. DHEA reversed reduced concentrations of many monoamines, particularly in the LH, in obese animals only. These latter changes provide indirect evidence to suggest that these central neurotransmitters may play an important role in the antiobesity effect of DHEA in the Zucker fatty rat.

[The influence of semen preparation and culture medium on the success of IVF in cattle]. / Der Einfluss von Samenaufbereitung und Kulturmedium auf den IVF-Erfolg beim Rind.

The effect of two semen-preparation methods and the presence and absence of capacitation-inducing supplements in the fertilization medium on IVF-results were examined in a 2 x 2 factorial design. In vitro matured oocytes were fertilized either with transmigrated (TM) or with swim-up (SU) prepared native semen. In the first group, the fertilization medium contained 0.8 microgram/ml heparin, 1.2 micrograms/ml hypotaurine and 0.2 microgram/ml epinephrine. However, in the second group, no capacitation-inducing or motility-enhancing substances were used. After SU-treatment, the supplements were necessary to obtain sufficient fertilization results. In the second group (non-supplemented medium), the percentages of penetrated and fertilized oocytes were decreased significantly (P < 0.001). By contrast, transmigrated semen required no additional supplementation of the fertilization medium. The penetration and fertilization rates of this semen-preparation method were equal in both groups.

Antiestrogen U23,469 induced alterations of catecholamine levels on plasma and central nervous system.

The effect of antiestrogen U23,469 administration in vivo on the concentration of dopamine, norepinephrine and epinephrine in the plasma, cerebral cortex and hypothalamus in ovariectomized rats was investigated. Rats were treated with estradiol benzoate, progesterone and U23,469 in different doses, s.c., daily for 6 days. Control group was injected with sesame oil. Catecholamines were estimated by radioenzymatic assay. Six days of U23,469, estradiol benzoate, progesterone or its combination altered the catecholamine levels compared to the control. Dopamine decreased in plasma with progesterone and U23,469. In the cerebral cortex, progesterone and U23,469 increased significantly and in the hypothalamus all the treatments produced a decrease of catecholamines. The levels of NE were reduced with estradiol benzoate, progesterone and U23,469; there was no significant difference in the norepinephrine levels after different treatments in the cerebral cortex, but the NE levels were significantly decreased in the hypothalamus. Epinephrine showed differences related to the treatment, as in plasma, as in cerebral cortex and hypothalamus. These results suggest that antiestrogen treatment compared with the estradiol benzoate or progesterone may affect the catecholamine levels of the central nervous system and plasma and support the idea that AE could have an indirect effect on the catecholaminergic system.

Biochemical resistance to development of morphine-dependence in rats: biogenic amines, its receptors and antibodies.

The level of norepinephrine (NE), epinephrine (E) and dopamine (DA) in hypothalamus and blood plasma along with antibodies to NE, DA and serotonin (5-HT) and characteristics of alpha 1-, alpha 2-adrenergic, D2-dopaminergic and S2-serotoninergic receptors in synaptic brain membranes were studied in two groups of rats predisposed or resistant to the formation of physical morphine dependence. The resistant animals were characterized by a significant elevation of DA levels in blood plasma, elevation of antibodies to NE, and by higher concentration of alpha 2-adrenergic receptors in the brain cortex and of D2-receptors in striatum. The affinity of D2-receptors to dopamine in resistant rats also was higher than in predisposed animals. The other parameters studied did not differ significantly between the two groups. These findings suggest that the increased activity of DA and NE neurotransmitter systems can be a cause for the genetic resistance of some individuals among Wistar rats to the formation of physical dependence on morphine.