Acute effects of barakol and serotonergic drugs on exploratory behaviour in rats

Barakol (10 mg/kg, i.p.), an active ingredient extracted from Cassia siamea, has been shown to have anxiolytic properties on the elevated plus-maze at a low dose similar to diazepam and to increase exploratory and locomotor behaviour. Drugs increasing serotonergic function also alter exploratory activity. The mechanism underlying the effects of barakol on exploratory behaviour has not been studied, therefore, the aim of the present study was to investigate exploratory activity in rats treated with barakol compared with drugs known to have specific action on the 5HT system. Exploratory behaviours were monitored in the rat using the holeboard model. The results show that the 5HT1A receptor agonist 8-OH-DPAT (1 mg/kg, i.p.) significantly (

Differences in peripheral noradrenergic function among actively drinking and abstinent alcohol-dependent individuals.

We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly higher in actively drinking alcohol-dependent subjects compared to those in remission and controls. While Type I and Type II alcoholic individuals differed across clinical measures, NA levels were similar in the two subtypes. Both subtypes showed an elevation in NA levels during active drinking compared to controls, but NA levels did not differ between the two subtypes and controls during remission. The findings indicate that chronic exposure to alcohol may lead to disturbances in NA activity that may manifest in early abstinence. However, the changes in NA activity appears to normalize after a longer period of abstinence. Alterations in NA activity do not seem to be specific for Type I or Type II subtypes of alcoholism

Dissociable Roles of Dopamine Within the Core and Medial Shell of the Nucleus Accumbens in Memory for Objects and Place

There is increasing focus on the role of the nucleus accumbens (NAc) in learning and memory, but there is little consensus as to how the core and medial shell subregions of the NAc contribute to these processes. In the current experiments, we used spontaneous object recognition to test rats with 6-hydroxydopamine lesions targeted at the core or medial shell of the NAc on a familiarity discrimination task and a location discrimination task. In the object recognition variant, control animals were able to discriminate the novel object at both 24-hr and 5-min delay. However, in the lesion groups, performance was systematically related to dopamine (DA) levels in the core but not the shell. In the location recognition task, sham-operated animals readily detected the object displacement at test. In the lesion groups, performance impairment was systematically related to DA levels in the shell but not the core. These results suggest that dopamine function within distinct subregions of the NAc plays dissociable roles in the modulation of memory for objects and place

Opposing effects of 5,7-DHT lesions to the core and shell of the nucleus accumbens on the processing of irrelevant stimuli

There is good evidence that forebrain serotonergic systems modulate cognitive flexibility. Latent inhibition (LI) is a cross-species phenomenon which manifests as poor conditioning to a stimulus that has previously been experienced without consequence and is widely considered an index of the ability to ignore irrelevant stimuli. While much research has focused on dopaminergic mechanisms underlying LI, there is also considerable evidence of serotonergic modulation. However, the neuroanatomical locus of these effects remains poorly understood. Previous work has identified the nucleus accumbens (NAc) as a key component of the neural circuit underpinning LI and furthermore, this work has shown that the core and shell subregions of the NAc contribute differentially to the expression of LI. To examine the role of the serotonergic input to NAc in LI, we tested animals with 5,7-dihydroxytryptamine (5,7-DHT) lesions to the core and shell subregions on LI assessed under experimental conditions that produce LI in shams and subsequently with weak stimulus pre-exposure designed to prevent the emergence of LI in shams. We found that serotonergic deafferentation of the core disrupted LI whereas 5,7-DHT lesions to the shell produced the opposite effect and potentiated LI

The effect of catecholaminergic depletion within the prelimbic and infralimbic medial prefrontal cortex on recognition memory for recency, location, and objects

There is good evidence that the medial prefrontal cortex (mPFC) is involved in different aspects of recognition memory. However, the mPFC is a heterogeneous structure, and the contribution of the prelimbic (PL) and infralimbic (IL) cortices to recognition memory has not been investigated. Similarly, the role of different neuromodulators within the mPFC in these processes is poorly understood. To this end, we tested animals with 6-hydroxydopamine (6-OHDA) lesions of the PL and IL mPFC on three tests of object recognition memory that required judgments about recency, object location, and object identity. In the recency task, lesions to both PL and IL severely impaired animals' ability to differentiate between old (earlier presented) and recently presented familiar objects. Relative to sham and PL animals, the IL lesion also disrupted performance on the object location task. However, both lesions left novel object recognition intact. These data confirm previous reports that the mPFC is not required for discriminations based on the relative familiarity of individual objects. However, these results demonstrate that catecholamines within the PL cortex are crucial for relative recency judgments and suggest a possible role for neural processing within the IL in the integration of information about object locatio

Evaluation of a novel Y-shaped extracardiac Fontan baffle using computational fluid dynamics

ObjectivesThe objective of this work is to evaluate the hemodynamic performance of a new Y-graft modification of the extracardiac conduit Fontan operation. The performance of the Y-graft design is compared to two designs used in current practice: a t-junction connection of the venae cavae and an offset between the inferior and superior venae cavae.MethodsThe proposed design replaces the current tube grafts used to connect the inferior vena cava to the pulmonary arteries with a Y-shaped graft. Y-graft hemodynamics were evaluated at rest and during exercise with a patient-specific model from magnetic resonance imaging data together with computational fluid dynamics. Four clinically motivated performance measures were examined: Fontan pressures, energy efficiency, inferior vena cava flow distribution, and wall shear stress. Two variants of the Y-graft were evaluated: an “off-the-shelf” graft with 9-mm branches and an “area-preserving” graft with 12-mm branches.ResultsEnergy efficiency of the 12-mm Y-graft was higher than all other models at rest and during exercise, and the reduction in efficiency from rest to exercise was improved by 38%. Both Y-graft designs reduced superior vena cava pressures during exercise by as much as 5 mm Hg. The Y-graft more equally distributed the inferior vena cava flow to both lungs, whereas the offset design skewed 70% of the flow to the left lung. The 12-mm graft resulted in slightly larger regions of low wall shear stress than other models; however, minimum shear stress values were similar.ConclusionsThe area-preserving 12-mm Y-graft is a promising modification of the Fontan procedure that should be clinically evaluated. Further work is needed to correlate our performance metrics with clinical outcomes, including exercise intolerance, incidence of protein-losing enteropathy, and thrombus formation

Antidepressant-like effects of Δ9-tetrahydrocannabinol and rimonabant in the olfactory bulbectomised rat model of depression

The endocannabinoid signalling system is widely accepted to play a role in controlling the affective state. Plant cannabinoids are well known to have behavioural effects in animals and humans and the cannabinoid CB1 receptor antagonist rimonabant has recently been shown to precipitate depression-like symptoms in clinical trial subjects. The aim of the present study was to investigate the behavioural and neurochemical effects of chronic administration of Δ9-tetrahydrocannabinol (THC) and rimonabant on intact and olfactory bulbectomised (OB) rats used as a model of depression. As expected, OB rats were hyperactive in the open field. Repeated THC (2 mg/kg, i.p. once every 48 h for 21 days) and rimonabant (5 mg/kg, i.p. once every 48 h for 21 days) reduced this hyperactivity, which is typical of clinically effective antidepressant drugs. In intact animals, chronic THC increased brain derived neurotrophic factor (BDNF) expression levels in the hippocampus and frontal cortex but rimonabant had no effect. Rimonabant increased the levels of phosphorylated extracellular signal regulated kinases (p-ERKs1/2) in the hippocampus and prefrontal cortex and THC also increased expression in frontal cortex. OB did not affect BDNF or p-ERK1/2 expression in the hippocampus or frontal cortex and in, contrast to the intact animals, neither THC nor rimonabant altered expression in the OB rats. These findings indicate antidepressant-like behavioural properties of both THC and rimonabant in OB rats although additional studies are required to clarify the relationship between the chronic effects of cannabinoids in other pre-clinical models and in human depression

Nonlinear quantum gravity on the constant mean curvature foliation

A new approach to quantum gravity is presented based on a nonlinear quantization scheme for canonical field theories with an implicitly defined Hamiltonian. The constant mean curvature foliation is employed to eliminate the momentum constraints in canonical general relativity. It is, however, argued that the Hamiltonian constraint may be advantageously retained in the reduced classical system to be quantized. This permits the Hamiltonian constraint equation to be consistently turned into an expectation value equation on quantization that describes the scale factor on each spatial hypersurface characterized by a constant mean exterior curvature. This expectation value equation augments the dynamical quantum evolution of the unconstrained conformal three-geometry with a transverse traceless momentum tensor density. The resulting quantum theory is inherently nonlinear. Nonetheless, it is unitary and free from a nonlocal and implicit description of the Hamiltonian operator. Finally, by imposing additional homogeneity symmetries, a broad class of Bianchi cosmological models are analyzed as nonlinear quantum minisuperspaces in the context of the proposed theory.Comment: 14 pages. Classical and Quantum Gravity (To appear

Asymptotics of the Wigner 9j symbol

We present the asymptotic formula for the Wigner 9j-symbol, valid when all quantum numbers are large, in the classically allowed region. As in the Ponzano-Regge formula for the 6j-symbol, the action is expressed in terms of lengths of edges and dihedral angles of a geometrical figure, but the angles require care in definition. Rules are presented for converting spin networks into the associated geometrical figures. The amplitude is expressed as the determinant of a 2x2 matrix of Poisson brackets. The 9j-symbol possesses caustics associated with the fold and elliptic and hyperbolic umbilic catastrophes. The asymptotic formula obeys the exact symmetries of the 9j-symbol.Comment: 17 pages, 7 figure