Aromatic Bromination Abolishes Deficits in Visuospatial Learning Induced by MDMA ("Ecstasy") in Rats While Preserving the Ability to Increase LTP in the Prefrontal Cortex.

It has recently been demonstrated that aromatic bromination at C(2) abolishes all typical psychomotor, and some key prosocial effects of the entactogen MDMA in rats. Nevertheless, the influence of aromatic bromination on MDMA-like effects on higher cognitive functions remains unexplored. In the present work, the effects of MDMA and its brominated analog 2Br-4,5-MDMA (1 mg/kg and 10 mg/kg i.

The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition.

A crucial etiological component in fetal programming is early nutrition. Indeed, early undernutrition may cause a chronic increase in blood pressure and cardiovascular diseases, including stroke and heart failure. In this regard, current evidence has sustained several pathological mechanisms involving changes in central and peripheral targets.

Prefrontal Cortical Control of Activity in Nucleus Accumbens Core Is Weakened by High-Fat Diet and Prevented by Co-Treatment with N-Acetylcysteine: Implications for the Development of Obesity.

A loss of neuroplastic control on nucleus accumbens (NAc) neuronal activity exerted by the medial prefrontal cortex (mPFC) through long-term depression (LTD) is involved in triggering drug-seeking behavior and relapse on several substances of abuse due to impaired glutamate homeostasis in tripartite synapses of the nucleus accumbens (NAc) core. To test whether this maladaptive neuroplastic mechanism underlies the addiction-like behavior induced in young mice by a high-fat diet (HFD), we utilized 28-days-old male mice fed HFD ad-libitum over 2 weeks, followed by 5 days of HFD abstinence. Control groups were fed a regular diet.

NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats.

Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.

Hypertension in Prenatally Undernourished Young-Adult Rats Is Maintained by Tonic Reciprocal Paraventricular-Coerulear Excitatory Interactions.

Prenatally malnourished rats develop hypertension in adulthood, in part through increased α-adrenoceptor-mediated outflow from the paraventricular nucleus (PVN) to the sympathetic system. We studied whether both α-adrenoceptor-mediated noradrenergic excitatory pathways from the locus coeruleus (LC) to the PVN and their reciprocal excitatory CRFergic connections contribute to prenatal undernutrition-induced hypertension. For that purpose, we microinjected either α-adrenoceptor or CRH receptor agonists and/or antagonists in the PVN or the LC, respectively.

Effects of Interleukin-1β in Glycinergic Transmission at the Central Amygdala.

Interleukin-1β (IL-1β) is an important cytokine that modulates peripheral and central pain sensitization at the spinal level. Among its effects, it increases spinal cord excitability by reducing inhibitory Glycinergic and GABAergic neurotransmission. In the brain, IL-1β is released by glial cells in regions associated with pain processing during neuropathic pain.

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.

Early postnatal environmental enrichment restores neurochemical and functional plasticities of the cerebral cortex and improves learning performance in hidden-prenatally-malnourished young-adult rats.

Moderate reduction of dietary protein (from 25% to 8% casein) in pregnant rats, calorically compensated by carbohydrates, gives rise to 'hidden prenatal malnutrition' (HPM) in the offspring since it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to decreased β-adrenoceptor signaling and brain derived neurotrophic factor (BDNF) levels in the pup' brain, altogether with defective cortical long-term potentiation (LTP) and lowered visuospatial memory performance. Since early postnatal environmental enrichment (EE) has been shown to exert plastic effects on the developing brain and neuroprotection both on cognition and on structural properties of the neocortex, in the present study we addressed the question of whether early postnatal EE during the lactation period could exert compensatory changes in the expression of ®-adrenergic receptors and BDNF in the neocortex of HPM rats, and if these effects are associated with an improvement or even a restore of both neocortical LTP in vivo and cognitive performance induced by HPM.

Facts and hypotheses about the programming of neuroplastic deficits by prenatal malnutrition.

Studies in rats have shown that a decrease in either protein content or total dietary calories results in molecular, structural, and functional changes in the cerebral cortex and hippocampus, among other brain regions, which lead to behavioral disturbances, including learning and memory deficits. The neurobiological bases underlying those effects depend at least in part on fetal programming of the developing brain, which in turn relies on epigenetic regulation of specific genes via stable and heritable modifications of chromatin. Prenatal malnutrition also leads to epigenetic programming of obesity, and obesity on its own can lead to poor cognitive performance in humans and experimental animals, complicating understanding of the factors involved in the fetal programming of neuroplasticity deficits.

Dark Classics in Chemical Neuroscience: Mescaline.

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T.

β2-adrenoceptor stimulation restores frontal cortex plasticity and improves visuospatial performance in hidden-prenatally-malnourished young-adult rats.

Moderate reduction in dietary protein composition of pregnant rats from 25% to 8% casein, calorically compensated by carbohydrates, has been described as a "hidden malnutrition" because it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to altered central noradrenergic systems, impaired cortical long-term potentiation (LTP) and worsened visuo-spatial memory performance. Given the increasing interest on the role played by β2-adrenoceptors (β2-ARs) on brain plasticity, the present study aimed to address the following in hidden-malnourished and eutrophic control rats: (i) the expression levels of β2-ARs in the frontal cortex determined by immunohistochemistry, and (ii) the effect of the β2 selective agonist clenbuterol on both LTP elicited in vivo in the prefrontal cortex and visuospatial performance measured in an eight-arm radial maze.

Preference for high-fat diet is developed by young Swiss CD1 mice after short-term feeding and is prevented by NMDA receptor antagonists.

Obesity is a worldwide epidemic that is increasing at an alarming rate. One of its causes is the increased availability and consumption of diets rich in fat. In the present study, we investigated the effects of short-term consumption of a high fat diet (HFD) on dietary preferences in Swiss CD1 mice and its relation in time to specific metabolic effects.

Knockdown of α2C-adrenoceptors in the occipital cortex rescued long-term potentiation in hidden prenatally malnourished rats.

Moderate reduction in the protein content of the mother's diet calorically compensated by carbohydrates (the so-called "hidden" prenatal malnutrition) leads to increased neocortical expression of the α(2C)-adrenoceptor subtype, together with decreased cortical release of noradrenaline and impaired long-term potentiation (LTP) and visuospatial memory performance during the rat postnatal life. In order to study whether overexpression of the α(2C)-adrenoceptor subtype is causally related to the decreased indices of neocortical plasticity found in prenatally malnourished rats, we evaluated the effect of intracortical (occipital cortex) administration of an antisense oligodeoxynucleotide (ODN) raised against the α(2C)-adrenoceptor mRNA on the LTP elicited in vivo in the occipital cortex of hidden prenatally malnourished rats. In addition, we compare the effect of the antisense ODN to that produced by systemical administration of the subtype-nonselective α(2)-adrenoceptor antagonist atipamezole.

Influence of protonation on substrate and inhibitor interactions at the active site of human monoamine oxidase-A.

Although substrate conversion mediated by human monoaminooxidase (hMAO) has been associated with the deprotonated state of their amine moiety, data regarding the influence of protonation on substrate binding at the active site are scarce. Thus, in order to assess protonation influence, steered molecular dynamics (SMD) runs were carried out. These simulations revealed that the protonated form of the substrate serotonin (5-HT) exhibited stronger interactions at the protein surface compared to the neutral form.

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.

Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.

2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.

[Pharmacokinetic comparison of Sinemet and Grifoparkin (levodopa/carbidopa 250/25 mg) in Parkinson s disease: a single dose study].

Background: There are doubts wether generic medications have the same bioavailability and efficacy compared with the original drugs developed by pharmaceutical companies with research capabilities.

Aim: To compare the pharmacokinetics and clinical (motor) responses of Sinemet and Grifoparkin (generic carbidopa/levodopa 250/25 mg) in patients with advanced Parkinson's disease.

Patients And Methods: Patients were randomly assigned to Sinemet (15 patients 62 +/- 12 years old; mean disease duration 11 +/- 7 years) or Grifoparkin (15 patients, 64 +/- 11 years old; mean disease duration 12 +/- 4 years) groups.