Effects of Beta; 1-adrenoceptors in the Basolateral Amygdala on Spatial Memory, Passive Avoidance, Long-term Potentiation and Neuronal Arborization in the Hippocampal CA1 Region in Response to Unavoidable Stress

Abstract Norepinephrine in the basolateral amygdala (BLA) plays a pivotal role in mediating the effects of stress on memory functions in the hippocampus, however, the functional contribution of β1-adrenergic receptors on the BLA inputs to the CA1 region of hippocampus and memory function are not well understood. In the present study the role of β1-adrenoreceptor in the BLA on memory, neuronal arborization and long-term potentiation (LTP) in the CA1 region of hippocampus was examined by infusion the β1-adrenoreceptor agonist (Dobutamine; 0.5µl/side) or antagonist (Atenolol; 0.25µL/side) bilaterally into the BLA before foot-shock stress. Passive avoidance test results showed that Step-through latency time was significantly decreased in the stress group rats one, four and seven days after the stress, which intra-BLA injection of Atenolol or Dobutamine before stress couldn't attenuate this reduction. Barnes-maze results revealed that infusion of Dobutamine and Atenolol significantly reduced spatial memory indicators such as increased latency time, the number of errors and the distance traveling to achieve the target hole in the stress group. These learning impairments in stress rats correlated with a reduction of LTP in hippocampal CA1 synapses in-vivo, which infusion of Dobutamine and Atenolol couldn't attenuate the population spike amplitude and mean-field excitatory postsynaptic potentials (fEPSP) slope reduction induced by stress. Also, the Golgi-Cox staining demonstrated that infusion of Atenolol attenuated stress decreased CA1 region dendritic and axonal arborization. These results suggest that β1-adrenergic receptors activation or block seem to exacerbate stress-induced hippocampal memory deficits and this effect is independent of CA1 LTP modulation.

Between the foreign and the local: French midwifery, traditional practitioners, and vernacular medical knowledge about childbirth in Lima, Peru / Entre o estrangeiro e o local: obstetrizes francesas, médicos tradicionais e conhecimento médico vernáculo sobre partos em Lima, Peru

This article examines the politics of midwifery and the persecution of untitled female assistants in childbirth in early republican Peru. A close reading of late colonial publications and the works of Benita Paulina Cadeau Fessel, a French obstetriz director of a midwifery school in Lima, demonstrates both trans-Atlantic and local influences in the campaign against untitled midwives. Cadeau Fessel's efforts to promote midwifery built upon debates among writers in Peru's enlightened press, who vilified untrained midwives' and wet nurses' vernacular medical knowledge and associated them with Lima's underclass. One cannot understand the transfer of French knowledge about professional midwifery to Peru without reference to the social, political, and cultural context.

Este artigo analisa as políticas de práticas de parteiras profissionais e a condenação de parteiras leigas nos primórdios do Peru republicano. A leitura atenta de publicações de fins do período colonial e dos trabalhos de Benita Paulina Cadeau Fessel, obstetriz francesa diretora de uma escola de parteiras em Lima, revela influência tanto transatlântica como local na campanha contra as parteiras sem titulação. Cadeau Fessel promovia seu ofício com base em debates veiculados na imprensa peruana ilustrada, que aviltavam o conhecimento tradicional de amas de leite e parteiras leigas e as associavam às classes desfavorecidas. Só é possível compreender a transferência do conhecimento francês sobre trabalho de parteiras profissionais para o Peru relacionando-a ao contexto social, político e cultural.

Estresse Isolado ou Associado ao Etanol Libera Prostanóides em Aorta de Ratos via ?2-Adrenoceptores / Stress Alone or associated with Ethanol Induces Prostanoid Release in Rat Aorta via ?2-Adrenoceptor

Fundamento: Estresse e etanol são ambos, independentemente, importantes fatores de risco cardiovascular. Objetivo: avaliar o risco cardiovascular do consumo de etanol e exposição ao estresse, isolados e em associação, em ratos machos adultos. Métodos: Os ratos foram separados em quatro grupos: controle, etanol (20% na água de beber durante seis semanas), estresse (imobilização 1h dia/5 dias por semana/ 6 semanas) e estresse/etanol. As curvas de concentração-resposta à noradrenalina - na ausência e na presença de ioimbina, L-NAME ou indometacina - ou fenilefrina foram determinadas em aortas torácicas com e sem endotélio. EC50 e resposta máxima (n = 8-12) foram comparadas através de ANOVA de dois fatores (two-way) / método de Bonferroni. Resultados: Estresse ou estresse em associação com o consumo de etanol aumentaram as respostas máximas de noradrenalina em aortas intactas. Essa hiper-reatividade foi eliminada pela remoção do endotélio, ou pela presença da indometacina ou ioimbina, mas não foi alterada pela presença de L-NAME. Enquanto isso, o consumo de etanol não alterou a reatividade à noradrenalina. As respostas da fenilefrina em aortas com e sem endotélio também permaneceram inalteradas independentemente do protocolo. Conclusão: O estresse crônico aumentou as respostas aórticas dos ratos à noradrenalina. Esse efeito é dependente do endotélio vascular e envolve a liberação de prostanóides vasoconstritores através da estimulação de α-2 adrenoceptores endoteliais. Além disso, o consumo crônico de etanol pareceu não influenciar as respostas de noradrenalina em aorta de rato, nem modificar o aumento de tais respostas observadas em consequência da exposição ao estresse. .

Background: Stress and ethanol are both, independently, important cardiovascular risk factors. Objective: To evaluate the cardiovascular risk of ethanol consumption and stress exposure, isolated and in association, in male adult rats. Methods: Rats were separated into 4 groups: Control, ethanol (20% in drinking water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and stress/ethanol. Concentration-responses curves to noradrenaline - in the absence and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were determined in thoracic aortas with and without endothelium. EC50 and maximum response (n=8-12) were compared using two-way ANOVA/Bonferroni method. Results: Either stress or stress in association with ethanol consumption increased the noradrenaline maximum responses in intact aortas. This hyper-reactivity was eliminated by endothelium removal or by the presence of either indomethacin or yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol consumption did not alter the reactivity to noradrenaline. The phenylephrine responses in aortas both with and without endothelium also remained unaffected regardless of protocol. Conclusion: Chronic stress increased rat aortic responses to noradrenaline. This effect is dependent upon the vascular endothelium and involves the release of vasoconstrictor prostanoids via stimulation of endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared to neither influence noradrenaline responses in rat thoracic aorta, nor did it modify the increase of such responses observed as a consequence of stress exposure. .

Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.

Progress on relationship between omega-3 polyunsaturated fatty acids and violent-aggressive behavior / 法医学杂志

The relationship between omega-3 polyunsaturated fatty acids (PUFAs) and violent-aggressive behavior has been payed attention since 1980s. Their correlation was explored by many epidemiological investigations, and the effect of PUFAs on prevention or reduction of violent-aggressive behavior in different groups were also affirmed by some intervention studies. This article summarized the previous studies and reviewed the history of epidemiological or intervention studies on PUFAs and its relationship with violent-aggressive behavior. It also presented the possible influencing factors in these studies and possible mechanisms.

Increased Cortisol after Stress is Associated with Variability in Response Time in ADHD Children

PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) often perform poorly during cognitive tests. We sought to evaluate cortisol as potential moderator of performance in mentally challenging tasks in children with ADHD. MATERIALS AND METHODS: Ninety clinic-referred children with ADHD were studied. Cortisol contents in saliva were measured before and after administration of a continuous performance test (CPT). RESULTS: Pre and post CPT cortisol levels were similar in 68 children. Children whose cortisol level increased after testing ( n = 22 ) displayed a significantly longer response time and increased response time variability scores as compared to children who did not display increase of cortisol after the CPT test. Even after controlling for the effects of response time and anxiety, the changes in cortisol levels were associated with effect on response time variability. CONCLUSION: The patients who showed an increased cortisol level after stress displayed a higher variability in response time than the patients who showed no change or a decreased cortisol level. The result of the current study suggests that stress-induced high norepinephrine (NE) release may accompany poorer attention performance in patients with ADHD.

CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats.

Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.

Effect of intracerebroventricular methotrexate on brain amines.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.

Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20 percent aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47 percent increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70 percent) and DA (50 and 36 percent) levels. On the other hand, increases were seen in 5-HIAA (146 and 153 percent) and 5-HT (59 and 86 percent) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129 percent) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61 percent). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

Central inhibitory effect of Moringa oleifera root extract: possible role of neurotransmitters.

Effect of chronic treatment of standardized aqueous extract of Moringa oleifera (MO) root (100, 200, 300, 350, 400, 450 mg/kg; po) on penicillin (PCN) induced convulsion, locomotor behaviour, brain serotonin (5-HTT), dopamine (DA) and norepinephrine (NE) level was studied in Holtzman strain adult albino rats. The result revealed that pretreatment with MO inhibited PCN-induced seizure and markedly reduced locomotor activity. Chronic treatment with MO significantly increased the 5-HT and decreased the DA level in cerebral cortex (CC), midbrain (MB), caudate nucleus (CN) and cerebellum (CB). NE level was significantly decreased in CC but no appreciable change was observed in MB, CB and CN. Thus the central inhibitory effect of MO is discussed in the light of the disturbed balance between 5-HT, DA and NE.

Stress hormones in the research on cardiovascular effects of noise.

In recent years, the measurement of stress hormones including adrenaline, noradrenaline and cortisol has been widely used to study the possible increase in cardiovascular risk of noise exposed subjects. Since endocrine changes manifesting in physiological disorders come first in the chain of cause-effect for perceived noise stress, noise effects in stress hormones may therefore be detected in populations after relatively short periods of noise exposure. This makes stress hormones a useful stress indicator, but regarding a risk assessment, the interpretation of endocrine noise effects is often a qualitative one rather than a quantitative one. Stress hormones can be used in noise studies to study mechanisms of physiological reactions to noise and to identify vulnerable groups. A review is given about findings in stress hormones from laboratory, occupational and environmental studies.

In Vivo Microdialysis Measures of Extracellular Norepinephrine in the Rat Amygdala during Sleep-wakefulness

Norepinephrine (NE)-containing locus ceruleus (LC) has been known to participate in the regulation of the sleep-wake cycle according to the differential firing rate. The aim of this study was to know the change of extracellular NE level in the rat amygdala, which are reciprocally connected with LC, during sleep-wake-fulness. Extracellular NE levels in the rat amygdala were inrestigated during different stages of the sleep-waking cycle using in vivo microdialysis and polygraphic recording. Dialysates were collected every 5 min and correlated with the results of polygraphic recording. The content of NE was measured by high-performance liquid chromatography with electrochemical detection. NE level was the highest in active waking (AW) and, when compared to AW, NE level was progressively lower in quiet waking (QW; 86%), quiet sleep (QS; 72%), and active sleep (AS or REM sleep; 61%). This result suggests that the rat amygdala also participates in the regulation of the sleep-wake cycle according to the differential NE release.

Role of dopamine in the modulation of adrenal gland responses in the osmotically stressed pigeons, Columba livia.

Salt loading on pigeons (C. livia) had stimulatory effects on brain amines (dopamine and 5-hydroxytryptamine), corticosterone, norepinephrine and epinephrine contents of adrenal gland. Conjoint administration of dopamine with hypertonic saline restored the brain amines and corticosterone of adrenal gland, but had no effect on catecholamine (CAM) contents of adrenal medulla. The excessive release of CAM in the plasma indicates sympathetic stimulation after both the treatments.

Does the release of tritiated noradrenaline accuratelly reflect the realease of endogenous noradrenaline from rat vas deferens nerve terminals?

To determine whether the release of tritiated noradrenaline (NA) from the sympathetic nerve terminals of the rat vas deferens is an accurate reflection of the release of endogenous NA, we compared the electrically-evoked release of tritiated and endogenous NA from the prostatic sections of the vasa deferentia of male rats. We found that while the release of tritiated NA was completely dependent on the presence of calcium, the release of endogenous NA was not. The overflow of both, tritiated and endogenous NA, was virtually unaffected by blockade of the neuronal uptake mechanism by desipramine. In contrast, blockade of the extraneuronal uptake greatly increased the overflow of endogenous NA, while having no effect on the overflow of tritiated NA. Tritiated NA release, on the other hand, was sensitive to prejunctional regulation, while the release of endogenous NA was not. Increases in stimulus train duration induced a significant increase in the release of endogenous NA, but not in that of tritiated NA. In contrast, the later responded to lower stimulus train frequencies and reached a plateau at lower frequency values as compared to the endogenous NA release. Our results indicate the existence of marked differences between the release of tritiated and endogenous NA. We conclude that: 1) the assumption that tritiated NA release provides a good marker for endogenous NA release in the rat was deferens seems unwarranted; 2) the use of endogenous NA to study the release process in the vas deferens requires a re-examination of the experimental conditions used, in order to minimize possible artifacts that may obscure the study of neuronal release; 3) the choice between measuring the release of tritiated or endogenous NA must be evaluated for each tissue in particular, taking into account its cytoarchitecture, as well as the experimental conditions used

Role of noradrenaline uptake inhibition and alpha-adrenoceptors in reperfusion ventricular arrhythmias in vivo and in vitro.

In view of the importance of sympathetic nervous system in the genesis of cardiac arrhythmias during reperfusion following coronary occlusion, the role of noradrenaline uptake inhibitor desipramine in the prevention of reperfusion arrhythmias was investigated in intact rabbit heart and isolated rat heart. For both the paradigms, ischaemia was produced by coronary artery ligation for 30 min followed by reperfusion for 60 min with drug administration at the time of reperfusion. Desipramine was used at three dose levels (0.2, 0.6 and 2.0 mg/kg) in the in vivo study while in vitro it was used at a concentration of 7 microM. Further, to investigate the status of adrenergic receptors during ischaemia and reperfusion, ischaemia was simulated by superfusing lactate physiological solution in isolated rabbit aortic strip preparation, which has well characterized alpha-receptors. Cumulative dose response curves (DRC) of selective alpha 1 agonist, phenylepherine (PE) were recorded during normal, ischaemic and reperfused conditions. Desipramine showed dose dependent anti-arrhythmic effect in vivo as well as in vitro. In intact heart studies desipramine offered protection against reperfusion arrhythmias in a dose related manner i.e. 50, 67.5 and 100% whereas in isolated studies, 50% protection was observed in the overall incidence of arrhythmias. DRC of PE shifted towards right during both ischaemia and reperfusion with a significant elevation of maximal response only during reperfusion.

Feocromocitoma: informe de un caso clínico y discusión de los procedimientos diagnósticos / Pheochromocytoma: a clinical case and revision of diagnostic procedures

Introducción. Los feocromocitomas son tumores que se originan en las células cromofines del sistema nervioso simpático y que se localizan en la médula suprarrenal. Liberan a la circulación epinefrina, norepinefrina o ambas, causando sintomatología adrenérgica. Caso clínico. Se presenta el caso de un escolar masculino con manifestaciones de hipersecreción adrenérgica caracterizada por cefalea, diaforesis, palpitaciones e hipertensión arterial severa. El laboratorio mostró niveles elevados de catecolaminas séricas y sus metabolitos urinarios. El ultrasonograma, la tomografía axial computada y la gamagrafía con I -MIBG demostraron tumores localizados en ambas suprarrenales, los cuales fueron extirpados exitosamente. Conclusiones. El diagnóstico de feocromocitoma debe sospecharse en base a los hallazgos clínicos y debe confirmarse con las determinaciones de catecolaminas y sus metabolismos urinarios. La extirpación quirúrgica del tumor no debe intentarse hasta no corroborar la localización exacta del mismo. Actualmente el método de localización específico y sensible es la gamagrafía con I -MIBG

Effect of neuropeptide FMRFamide on immobile behavior in rats.

In the forced swimming induced immobility test, neuropeptide FMRFamide (5-20 micrograms) administered via the intracerebroventricular (icv) route, prolonged immobilization period in rats. On the other hand, immunoneutralization of endogenous FMRFamide by its antiserum (1 microliter, icv) significantly reduced the duration of immobility. Intraperitoneal administration of amitriptyline (3 mg/kg), imipramine (5 mg/kg), fluoxetine (5 mg/kg) or amphetamine (0.5 mg/kg) attenuated FMRFamide-induced prolongation of immobility. Biochemical studies indicated that FMRFamide treatment had significant effects on rat brain monoamines. FMRFamide significantly lowered the brain levels of 5-hydroxytryptamine and norepinephrine in the doses that prolonged the immobility. These results that FMRFamide prolongs the duration of immobility, perhaps by modulating the release of neurotransmitters like 5-hydroxytryptamine and/or norepinephrine.

Central noradrenergic hyperactivity early in life: a hypothesis on the origin of morpho-functional brain disorders induced by malnutrition

Many studies have revealed that malnutrition, caused either by insufficient or unbalanced diet, during early stages of growth and development could result in a variety of morpho-functional brain disturbances, whose severity depends on the time of onset, duration and intensity of the nutritional injury. Nevertheless, little is known about the intimate mechanisms by which early malnutrition impairs brain structure and function. This article reviews evidence showing that (i) developmental malnutrition induces central noradrenergic hyperactivity, (ii) noradrenaline exerts a trophic role during brain development, and (iii) pharmacological reduction of central noradrenergic hyperactivity prevents malnutrition-induced functional brain disturbances

Effects of DSP-4-induced depletion of brain norepinephrine on appetitive and aversive memory retrieval.

This study examined whether depletion of central norepinephrine produces an improved retrieval of aversive memories in the same way as pre-exposure to inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given a single dose of DSP-4 (100, 200 or 400 micrograms/rat) or drug vehicle ICV 24 hr later. The retention performance and activity were assessed 48 hr after the treatment with this neurotoxin. DSP-4 had no effect on open field activities but enhanced latencies to enter both, previously shocked and appetitively reinforced, goalboxes. The data thus, suggest that central administration of DSP-4 does not result in selective enhanced aversive memories. On the contrary, post-trial NE depletion with this neurotoxin might interfere with the retrieval of previously learned association with appetitive stimuli. DSP-4 significantly reduced monoamines, depending upon the brain regions assayed and the doses studied. However, only decreased NE in striatum coincided with the memory changes suggesting that NE innervation to striatum may participate in the retrieval process.