A robust model of Stimulus-Specific Adaptation validated on neuromorphic hardware.

Stimulus-Specific Adaptation (SSA) to repetitive stimulation is a phenomenon that has been observed across many different species and in several brain sensory areas. It has been proposed as a computational mechanism, responsible for separating behaviorally relevant information from the continuous stream of sensory information. Although SSA can be induced and measured reliably in a wide variety of conditions, the network details and intracellular mechanisms giving rise to SSA still remain unclear.

Clenbuterol activates the central IL-1 system via the β2-adrenoceptor without provoking inflammatory response related behaviours in rats.

The long-acting, highly lipophilic, β2-adrenoceptor agonist clenbuterol may represent a suitable therapeutic agent for the treatment of neuroinflammation as it drives an anti-inflammatory response within the CNS. However, clenbuterol is also known to increase the expression of IL-1β in the brain, a potent neuromodulator that plays a role in provoking sickness related symptoms including anxiety and depression-related behaviours. Here we demonstrate that, compared to the immunological stimulus lipopolysaccharide (LPS, 250μg/kg), clenbuterol (0.

Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function.

There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders.

Metabolic, hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects.

Objectives: To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects.

Methods: Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS(E)), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis.

Results: This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic-pituitary-adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H.

Abnormalities in metabolism and hypothalamic-pituitary-adrenal axis function in schizophrenia.

For decades, evidence has been emerging that the pathogenesis of schizophrenia can involve perturbations in metabolic and hypothalamic-pituitary-adrenal (HPA) axis pathways. Variations in manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response, including the finding that a high proportion of subjects fail to respond to current antipsychotic medications. Here, we review the evidence for abnormalities in metabolism and HPA axis regulation in schizophrenia.

Proteomic technologies for biomarker studies in psychiatry: advances and needs.

In the postgenome era, proteomics has arisen as a promising tool for more complete comprehension of diseases and for biomarker discovery. Some of these objectives have already been partly achieved for illnesses such as cancer. In the case of psychiatric conditions, however, proteomic advances have had a less profound impact.

Dopamine D1 receptor-mediated intracellular responses in the hypothalamus after co-administration of caffeine with MDMA.

Markers of dopamine D(1) receptor activation were determined to elucidate intracellular mechanisms associated with the combined effects of caffeine and 3,4 methylenedioxymethamphetamine (MDMA), reported previously to produce increased toxicity, when compared with either drug alone. Caffeine (10 mg/kg) and MDMA (15 mg/kg) were administered to male Sprague Dawley rats alone and in combination. One hour after drug administration, core body temperature and phosphorylation of the dopamine D(1) -related intracellular markers, cAMP response element binding protein (CREB), the dopamine and c-AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and expression of the immediate early gene and cellular activation marker c-fos were determined in the hypothalamus.

A role for adenosine A(1) receptor blockade in the ability of caffeine to promote MDMA "Ecstasy"-induced striatal dopamine release.

Co-administration of caffeine profoundly enhances the acute toxicity of 3,4 methylenedioxymethamphetamine (MDMA) in rats. The aim of this study was to determine the ability of caffeine to impact upon MDMA-induced dopamine release in superfused brain tissue slices as a contributing factor to this drug interaction. MDMA (100 and 300μM) induced a dose-dependent increase in dopamine release in striatal and hypothalamic tissue slices preloaded with [(3)H] dopamine (1μM).

Caffeine promotes dopamine D1 receptor-mediated body temperature, heart rate and behavioural responses to MDMA ('ecstasy').

Rationale: Caffeine exacerbates the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') in rats characterised by hyperthermia, tachycardia and lethality. Depletion of central catecholamine stores and dopamine D(1) receptor blockade have been reported to attenuate the ability of caffeine to exacerbate MDMA-induced hyperthermia.

Objectives: Here, we investigate whether dopamine D(1) and D(2) receptors mediate the effects of caffeine on MDMA-induced changes in body temperature, heart rate and locomotor activity.