Regulation of conditioned and unconditioned fear in rats by 5-HT1A receptors in the dorsal periaqueductal gray

Studies on the involvement of 5-HT1-mediated mechanisms in the dorsal periaqueductal gray (dPAG) of animals with past stressful experiences have not been conducted so far. We investigated the role of 5-HT1 receptors in the dPAG of rats previously submitted to contextual fear conditioning. Defensive behaviors induced by activation of the dPAG were assessed by measuring the lowest electric current applied to this structure (threshold) able to produce freezing and escape responses during testing sessions of contextual fear conditioning, in which animals were placed in a context previously paired to footshocks. The 5-HT1A function of the dPAG was evaluated by local injections of 8-OH-DPAT (4 and 8 nmol/0.2 mu L) and WAY-100635 (10 nmol/0.2 mu L), selective agonist and antagonist of 5-HT1A receptors, respectively. In accordance with previous studies, 8-OH-DPAT increased aversive thresholds (antiaversive effects) but injections of WAY 100635 into the dPAG did not produce significant effects on the aversive thresholds in naive rats. However, the aversive thresholds of animals exhibiting contextual fear remained unchanged with both treatments. Moreover, 8-OH-DPAT and WAY 100635 did not change the dPAG post-stimulation freezing. The present results suggest that the stressful experience of being fear conditioned has an effect on the role of the 5-HT1A receptors in mediating unconditioned fear. Also, the reduction in the regulation of the defensive behaviors by 5-HT1A-mediated mechanisms in the dPAG of these animals may underlie the stress precipitated psychopathology associated with the neural substrates of aversion of the dPAG. (c) 2007 Elsevier Inc. All rights reserved.

Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

Background and objectives: Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. Design, setting, participants, and measurements: Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). Results: At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. Conclusions: This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes. Clin J Am Soc Nephrol 5: 286-291, 2010. doi: 10.2215/CJN.05420709

Dating the dreaming? Creation of myths and rituals for mounds along the northern Australian coastline

Shell mounds ceased to be built in many parts of coastal northern Australia about 800-600 years ago. They are the subject of stories told by Aboriginal people and some have been incorporated in ritual and political activities during the last 150 ears. These understandings emerged only after termination of the economic and environmental system that created them, 800-600 years ago, in a number of widely separated coastal regions, Modern stories and treatments of these mounds by Aboriginal people concern modern or near-modern practices. Modern views of the mounds, their mythological and ritual associations, may be explained by reference to the socioeconomic transitions seen in the archaeological record; but the recent cultural, social and symbolic statements about these places cannot inform us of the process or ideology concerned with the formation of the mounds. Many Aboriginal communities over the last half a millennium actively,formed understandings of new landscapes and systems of land use. Attempts to impose historic ideologies and cosmologies on earlier times fail to acknowledge the magnitude and rate of economic and ideological change on the tropical coastline of Australia.

Comparative effects of ageing and dementia of the Alzheimer type on orientation of visual attention

Age-related changes and the effects of dementia of the Alzheimer type (DAT) were investigated during a visual orienting attention task in which attention was pre-cued to one or other hemifields. Central cues were either valid, neutral, invalid or NoGo (inhibitory). The response time cost-benefit analysis showed a decreased benefit after valid cueing in the old compared with the young group with no change in the cost of invalid cueing. The older group were also slower over all cue types. These results suggest there is an age-related reduced ability to covertly orient attention in a visual hemifield before target onset. In contrast, the DAT group showed an increased response time benefit and showed a trend for a decreased cost in response time compared with controls. This was due to slowest response times after neutral cues. They also made significantly more response errors particularly following neutral cueing, and were less able to inhibit responses on NoGo trials than controls. The increased benefit and reduced cost found in the DAT group was interpreted as an impairment in dividing attention between left and right target locations.

Influence of silence and attention on tinnitus perception

OBJECTIVE: The purpose of this study was to study the effect of attention and sustained silence on the emergence of auditory phantom perception in normal-hearing adults. STUDY DESIGN: Cross-sectional survey. SUBJECTS AND METHODS: While sitting in a sound booth, 66 volunteers (age range. 18-65; mean age, 37.3) performed 3 experiments of 5 minutes each, consecutively and randomly presented. Two deviated attention from auditory system (Hanoi and visual attention experiments). and 1 drove attention to the auditory system (auditory attention). After each experiment, participants were asked about their auditory and visual perception. No sound or light change was given at any moment. RESULTS: Of the participants, 19.7% experienced tinnitus during Hanoi, 45.5% during visual attention, and 68.2% during auditory attention experiment. with no significant differences for studied variables. CONCLUSION: Tinnitus-like perceptions may occur in a non-clinical population in a silent environment. Concomitant auditory attention plays an important role on the emergence of tinnitus. (C) 2008 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

The love of a sage or the command of a superior: The natural law doctrines of Leibniz and Pufendorf

The study of natural law theories is presently one of the most fruitful areas of research in the studies of early modern intellectual history, and moral and political theory. Likewise the historical significance of the Enlightenment for the development of modernisation' in many different forms continues to be the subject of controversy. This collection therefore offers a timely opportunity to re-examine both the coherence of the concept of an early Enlightenment', and the specific contribution of natural law theories to its formation. The works of major thinkers such as Grotius, Hobbes, Locke, Malebranche, Pufendorf and Thomasius are reassessed, and the appeal and importance of the discourse of natural jurisprudence both to those working inside conventional educational and political structures and to those outside - such as in the Huguenot diaspora - is evaluated. This volume will therefore be of importance to all those readers concerned to study the character of the debates in the period 1650-1750 surrounding moral and political agency, sovereignty and obligation, and the legitimation of religious toleration in the divergent states and patriotic contexts of Europe.

Characterization of juvenile and young adult mice following induction of hydrocephalus with kaolin

Hydrocephalus is a common neurological problem in humans, Usually caused by an impairment of cerebrospinal fluid (CSF) flow or absorption. A reliable induced model of chronic hydrocephalus in mice would be useful to test hypotheses using genetic mutants. Our goal was to characterize behavioral and histological changes in juvenile and Young adult mice with kaolin (aluminum silicate) -induced hydrocephalus. Seven-day old and 7-8 week old mice received injection of kaolin into the cisterna magna. Behavior was assessed repeatedly. Seven or 14 days following kaolin, magnetic resonance (MR) imaging was used to assess ventricle size. In hydrocephalic mice, body weight was significantly lower than in age-matched saline-injected sham controls and the gait and posture score were impaired. Juvenile mice developed severe ventriculomegaly and had reduced corpus callosum thickness with gross white matter destruction by 14 days. Reactive astroglial change in white matter and cortex and reduced cellular proliferation in the subependymal zone were also apparent. Young adult mice developed only moderate ventricular enlargement without overt white matter destruction, although there was corpus callosum atrophy and mild astroglial reaction in white matter. Glial fibrillary acidic protein content was significantly higher in juvenile and young adult hydrocephalic mice at 7 and 14 days, but myelin basic protein content was not significantly altered. In conclusion, hydrocephalus induced by percutaneous injection of kaolin in juvenile and young adult mice is feasible. The associated periventricular alterations are essentially the same as those reported in rats of comparable ages. (C) 2009 Elsevier Inc. All rights reserved.

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Delta 9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis

Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting: University research center. Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.

Influence of pregnancy and smoking on brachial artery flow-mediated dilation values and time until maximum response

To evaluate the effect of pregnancy and smoking on endothelial function using brachial artery flow-mediated dilation (FMD) and to determine the time necessary until the occurrence of maximum brachial artery dilation after stimulus. This study was an observational study evaluating 133 women, who were grouped as follows: non-smoking pregnant women (N = 47), smoking pregnant women (N = 33), non-smoking women (N = 34), and smoking pregnant women (N = 19). The diameter of the brachial artery was measured at baseline and at 30, 60, 90 and 120 s after stimulus. The relative change of brachial artery was determined for each of these four moments. FMD measured at 60 s after stimulus was compared between the groups. The maximum FMD was observed at 60 s after cuff release in all groups. FMD was greater among non-smoking pregnant women compared to smoking pregnant women (11.50 +/- A 5.77 vs. 8.74 +/- A 4.83; p = 0.03) and also between non-smoking non-pregnant women compared to smoking non-pregnant women (10.52 +/- A 4.76 vs. 7.21 +/- A 5.57; p = 0.03). Maximum FMD was observed approximately 60 s after stimulus in all groups regardless of smoking and pregnancy status. The smoking habit seems to lead to endothelial dysfunction both in pregnant and non-pregnant women, as demonstrated by the lower FMD in smokers.

Comparison of the effects of aerobic and resistance training on cardiac autonomic adaptations in ovariectomized rats

We have compared the effects of two types of physical training on the cardiac autonomic control in ovariectomized and sham-operated rats according to different approaches: double autonomic blockade (DAB) with methylatropine and propranolol; baroreflex sensibility (BRS) and spectral analysis of heart rate variability (HRV). Wistar female rats (+/- 250 g) were divided into two groups: sham-operated and ovariectomized. Each group was subdivided into three subgroups: sedentary rats, rats submitted to aerobic trained and rats submitted to resistance training. Ovariectomy did not change arterial pressure, basal heart rate (HR), DAB and BRS responses, but interfered with HRV by reducing the low-frequency oscillations (LF = 0.20-0.75 Hz) in relation to sedentary sham-operated rats. The DAB showed that both types of training promoted an increase in the predominance of vagal tonus in sham-operated rats, but HR variations due to methylatropine were decreased in the resistance trained rats compared to sedentary rats. Evaluation of BRS showed that resistance training for sham-operated and ovariectomized rats reduced the tachycardic responses in relation to aerobic training. Evaluation of HRV in trained rats showed that aerobic training reduced LF oscillations in sham-operated rats, whereas resistance training had a contrary effect. In the ovariectomized rats, aerobic training increased high frequency oscillations (HF = 0.75-2.5 Hz), whereas resistance training produced no effect. In sham-operated rats, both types of training increased the vagal autonomic tonus, but resistance training reduced HF oscillations and BRS as well. In turn, both types of training had similar results in ovariectomized rats, except for HRV, as aerobic training promoted an increase in HF oscillations. (C) 2011 Elsevier B.V. All rights reserved.

Co-Expression of Leptin and Oestrogen Receptors in the Preoptic-Hypothalamic Area

The interaction between the reproductive axis and energy balance suggests that leptin acts as a possible mediator. This hormone acts in the regulation of metabolism, feeding behaviour and reproduction. Animals homozygous for the gene `ob` (ob/ob) are obese and infertile, and these effects are reversed after systemic administration of leptin. Thus, the present study aimed to determine: (i) whether cells that express leptin also express oestrogen receptors of type-alpha (ER-alpha) or -beta (ER-beta) in the medial preoptic area (MPOA) and in the arcuate (ARC), dorsomedial (DMH) and ventromedial hypothalamic nucleus and (ii) whether there is change in the gene and protein expression of leptin in these brain areas in ovariectomised (OVX) animals when oestrogen-primed. Wistar female rats with normal oestrous cycles or ovariectomised oestrogen-primed or vehicle (oil)-primed were utilised. To determine whether there was a co-expression, immunofluorescence was utilised for double staining. Confocal microscopy was used to confirm the co-expression. The technique of real-time polymerase chain reaction and western blotting were employed to analyse gene and protein expression, respectively. The results obtained showed co-expression of leptin and ER-alpha in the MPOA and in the DMH, as well as leptin and ER-beta in the MPOA, DMH and ARC. However, we did not detect leptin in the MPOA, ARC and DMH using western blotting and there was no statistical difference in leptin gene expression in the MPOA, DMH, ARC, pituitary or adipose tissue between OVX rats treated with oestrogen or vehicle. In conclusion, the results obtained in the present study confirm that the brain is also a source of leptin and reveal co-expression of oestrogen receptors and leptin in the same cells from areas related to reproductive function and feeding behaviour. Although these data corroborate the previous evidence obtained concerning the interaction between the action of brain leptin and reproductive function, the physiological relevance of this interaction remains uncertain and additional studies are necessary to elucidate the exact role of central leptin.