Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats.

Several lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions.

Aromatic Bromination Abolishes the Psychomotor Features and Pro-social Responses of MDMA ("Ecstasy") in Rats and Preserves Affinity for the Serotonin Transporter (SERT).

The entactogen MDMA (3,4-methylenedioxy-methamphetamine, "Ecstasy") exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulation of typical entactogenic effects, using analogs derived from the MDMA template, are still not fully understood. Among many possibilities, aromatic halogenation of the phenylalkylamine moiety may favor distribution to the brain due to increased lipophilicity, and sometimes renders psychotropic substances of high affinity for their molecular targets and high potency in humans.

Hippocampal Memory Recovery After Acute Stress: A Behavioral, Morphological and Molecular Study.

Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated-at the same time-the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in -methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits.

[Longitudinal perception of the educational environment in two medical schools with traditional curricula in Chile and Spain].

Background: To establish an educational environment that ensures the quality of the teaching-learning process is a challenge for any educational institution. The questionnaire DREEM (Dundee Ready Educational Environment Measure) is used to identify strengths and weaknesses of an educational environment and to compare different medical schools.

Aim: To evaluate the changes in the perception of educational environment by students of the Schools of Medicine of the University of Zaragoza, UZar (Spain) and the University of Chile, UCh (Chile) at two points in their curricula.

On the Role of DT-Diaphorase Inhibition in Aminochrome-Induced Neurotoxicity In Vivo.

Dopamine oxidation in the pathway leading to neuromelanin formation generates the ortho-quinone aminochrome, which is potentially neurotoxic but normally rapidly converted by DT-diaphorase to nontoxic leukoaminochrome. However, when administered exogenously into rat striatum, aminochrome is able to produce damage to dopaminergic neurons. Because of a recent report that substantia nigra pars compacta (SNpc) tyrosine hydroxylase (T-OH) levels were unaltered by aminochrome when there was cell shrinkage of dopaminergic neurons along with a reduction in striatal dopamine release, the following study was conducted to more accurately determine the role of DT-diaphorase in aminochrome neurotoxicity.

The ROCK Inhibitor Fasudil Prevents Chronic Restraint Stress-Induced Depressive-Like Behaviors and Dendritic Spine Loss in Rat Hippocampus.

Background: Dendritic arbor simplification and dendritic spine loss in the hippocampus, a limbic structure implicated in mood disorders, are assumed to contribute to symptoms of depression. These morphological changes imply modifications in dendritic cytoskeleton. Rho GTPases are regulators of actin dynamics through their effector Rho kinase.

Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease.

L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons.

Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons.

Chronic stress promotes cognitive impairment and dendritic spine loss in hippocampal neurons. In this animal model of depression, spine loss probably involves a weakening of the interaction between pre- and postsynaptic cell adhesion molecules, such as N-cadherin, followed by disruption of the cytoskeleton. N-cadherin, in concert with catenin, stabilizes the cytoskeleton through Rho-family GTPases.

Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker.

Background: Clinically depressed individuals respond to different types of antidepressants, suggesting that different neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not yet available.

Methods: We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or immobilization in adaptable plastic cones.

Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats.

Prenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy.

Repetitive fluoxetine treatment affects long-term memories but not learning.

Fluoxetine is currently being administered for long-term maintenance and for prophylactic reasons following the remission of depressive symptoms and several other psychiatric and neurological conditions. We have previously found that in naïve adult male rats, repetitive administration of fluoxetine induced maturation of telencephalic dendritic spines. This finding was associated with the presence of a higher proportion of GluA2- and GluN2A-containing glutamate receptors.

Behavioral profiles in rats distinguish among "ecstasy," methamphetamine and 2,5-dimethoxy-4-iodoamphetamine: Mixed effects for "ecstasy" analogues.

3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a psychoactive drug structurally related to other phenylisopropylamines acting as stimulants or hallucinogens in humans. Although MDMA has a pharmacological identity of its own, the distinction of its acute effects from those of stimulants or even hallucinogens is controversial. In this work, dose-response curves (0.

Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection.

Extracellular signal-regulated kinases (ERKs) are widely implicated in multiple physiological processes. Although ERK1/2 has been proposed as a common mediator of antidepressant action in naive rodents, it remains to be determined whether the ERK1/2 pathway plays a role in depressive disorder. Here, we investigated whether chronic restraint stress (14 days) and antidepressant treatment [desipramine (DMI), 10 mg/kg intraperitoneally] induce changes in animal behavior and hippocampal levels of phospho-ERK1/2 and its substrate phospho-cAMP response element-binding protein (CREB).

Chronic stress induces dendritic atrophy in the rat medial geniculate nucleus: effects on auditory conditioning.

Chronic stress induces dendritic atrophy in the inferior colliculus (IC, auditory mesencephalon) and impairs auditory avoidance conditioning. The aim of this study was to determine in Golgi preparations and in cued fear conditioning whether stress affects other auditory components, like the thalamic medial geniculate nucleus (MG) or the posterior thalamic nucleus (PO), in Sprague-Dawley rats. Chronic restraint stress produced a significant dendritic atrophy in the MG (stress: 407+/-55 microm; control: 808+/-120 microm; p<0.

Copper neurotoxicity in rat substantia nigra and striatum is dependent on DT-diaphorase inhibition.

The dependence of copper neurotoxicity on DT-diaphorase inhibition was suggested from results obtained from a cell line derived from substantia nigra. Therefore, the aim of this study was to evaluate whether CuSO4 neurotoxicity in vivo, which was evaluated by determining the contralateral rotation and loss of tyrosine hydroxylase immunostaining, was dependent on DT-diaphorase inhibition by dicoumarol. Animals unilaterally and intranigrally injected with 0.

Chronic stress induces upregulation of brain-derived neurotrophic factor (BDNF) mRNA and integrin alpha5 expression in the rat pineal gland.

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. Moreover, stress induces deleterious actions on the epithalamic pineal organ, a gland involved in a wide range of physiological functions.

Chronic stress decreases the expression of sympathetic markers in the pineal gland and increases plasma melatonin concentration in rats.

Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic-related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay.

Antidepressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans.

Salvia elegans Vahl (Lamiaceae), popularly known as "mirto", is a shrub that has been widely used in Mexican traditional medicine for the treatment of different central nervous system (CNS) diseases, principally, anxiety. Nevertheless, the available scientific information about this species is scarce and there are no reports related to its possible effect on the CNS. In this work, the antidepressant and anxiolytic like effects of hydroalcoholic (60%) extract of Salvia elegans (leaves and flowers) were evaluated in mice.

Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl-p-methoxyamphetamine derivatives.

The analgesic effects of (+)- and (-)-amphetamine (AMPH), (+/-)-p-methoxyamphetamine (MA), (+/-)-N-methyl-p-methoxyamphetamine (MMA) and (+/-)-N-ethyl-p-methoxyamphetamine (EMA) were compared using two different algesimetric tests in rats. In the formalin test, (+)-AMPH elicited significant antinociception at doses of 0.2, 2 and 8 mg/kg (i.

Behavioral effects of manganese injected in the rat substantia nigra are potentiated by dicumarol, a DT-diaphorase inhibitor.

The purpose of this study was to evaluate the contribution of DT-diaphorase inhibition to in vivo neurodegenerative effects of dopamine (DA) oxidation to the corresponding o-quinones. The neurotoxicity to nigrostriatal DA neurons was induced by injection of manganese pyrophosphate (Mn(3+)) complex as a prooxidizing agent alone or together with the DT-diaphorase inhibitor dicumarol into the right rat substantia nigra. The behavioral effects were compared with those induced after selective lesions of dopaminergic neurons with 6-hydroxydopamine (6-OHDA).