Riluzole increases glutamate uptake by cultured C6 astroglial cells.

Riluzole is a drug approved for the treatment of amyotrophic lateral sclerosis (ALS) and may be effective for the treatment of other neurodegenerative and neuropsychiatric disorders. Riluzole exerts diverse actions on the central nervous system, including altering glutamate release and uptake, and therefore act diminishing glutamate extracellular levels, but the underlying mechanism of these actions is still unknown. Here, we demonstrate that riluzole stimulated glutamate uptake and augmented the expression of the glutamate EAAC1 transporter in C6 astroglial cell cultures.

Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice.

Consumption of caffeine, an adenosine receptor antagonist, was found to be inversely associated with the incidence of Alzheimer's disease. Moreover, caffeine protects cultured neurons against beta-amyloid-induced toxicity, an effect mimicked by adenosine A(2A) but not A(1) receptor antagonists. We now tested if caffeine administration would prevent beta-amyloid-induced cognitive impairment in mice and if this was mimicked by A(2A) receptor blockade.

Beta-amyloid treatment sensitizes mice to amphetamine-induced locomotion but reduces response to caffeine.

Background: Psychosis frequently occurs in Alzheimer's disease (AD), being associated with more severe cognitive decline, but the underlying mechanisms are unknown.

Objective: To investigate the effect of centrally administered beta-amyloid peptide, a model for AD, in the locomotor response to amphetamine, caffeine and MK-801, which are psychoactive drugs related to neurochemical changes occurring in psychosis.

Methods: Mice were intracerebroventricularly injected with beta-amyloid (25-35), and after 1 week they were tested in the passive avoidance, spontaneous alternation and locomotor tasks.

Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications.

Based on the neuromodulatory and homeostatic actions of adenosine, adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. The present model of adenosine dysfunction in schizophrenia takes into consideration the dopamine and glutamate hypotheses, since adenosine exerts neuromodulatory roles on these systems, and proposes that adenosine plays a role in the inhibitory deficit found in schizophrenia. Given the role of adenosine activation of adenosine A1 receptor (A1R) in mediating neurotoxicity in early stages of brain development, pre- and peri-natal complications leading to excessive adenosine release could induce primary brain changes (i.

Cinnarizine has an atypical antipsychotic profile in animal models of psychosis.

Cinnarizine, a drug known as a calcium channel blocker, is currently used for the treatment of migraine and vertigo. Induction of extrapyramidal signs by cinnarizine has been reported in the elderly, which is related to its moderate antagonistic properties at dopamine D2 receptors, resembling the mechanism of action of most antipsychotic drugs. Despite this effect, cinnarizine has never been tested as a putative antipsychotic drug.

Behavioral and cognitive profile of mice with high and low exploratory phenotypes.

Temperament is the heritable and relatively stable pattern of basic emotions, such as fear and anger. We explored behavioral features in mice to select distinct phenotypes with extremes of temperament. In a new environment (open-field) with a central object, two groups of 15 mice from 79 screened were separated according to high or low exploration of the object to compose the high and low exploratory groups, respectively.

Guanosine selectively inhibits locomotor stimulation induced by the NMDA antagonist dizocilpine.

Guanosine has been shown to modulate glutamate system by stimulating astrocytic glutamate uptake. Recent evidence suggest that the locomotor effects of NMDA receptor antagonists, an animal model of schizophrenia, is associated with activation of non-NMDA glutamatergic receptors caused by increased glutamate release. The present work was undertaken to evaluate whether guanosine could have influence on the hyperlocomotion induced in mice by dizocilpine (MK-801), a NMDA antagonist.

Atypical antipsychotic profile of flunarizine in animal models.

Rationale: Flunarizine is known as a calcium channel blocker commonly used in many countries to treat migraine and vertigo. Parkinsonism has been described as one of its side-effects in the elderly, which is in agreement with its recently characterized moderate D2 receptor antagonism.

Objectives: To perform a pre-clinical evaluation of flunarizine as a potential antipsychotic.

Effect of riluzole on MK-801 and amphetamine-induced hyperlocomotion.

N-methyl-D aspartate (NMDA) antagonists, such as MK-801, and the dopamine indirect agonist amphetamine are pharmacological models used for the evaluation of putative new treatments for schizophrenia. Since the psychotomimetic effects of NMDA antagonists have recently been linked to their ability to increase glutamate release and since the glutamate release inhibitor riluzole prevented NMDA antagonist neurotoxicity, we evaluated the effect of riluzole on hyperlocomotion induced by MK-801 (0.25 mg/kg) and amphetamine (2.

Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity.

Adenosine is a neuromodulator in the nervous system and it has recently been observed that pharmacological blockade or gene disruption of adenosine A(2A) receptors confers neuroprotection under different neurotoxic situations in the brain. We now observed that coapplication of either caffeine (1-25 micro M) or the selective A(2A) receptor antagonist, 4-(2-[7-amino-2(2-furyl)(1,2,4)triazolo (2,3-a)(1,3,5)triazin-5-ylamino]ethyl)phenol (ZM 241385, 50 nM), but not the A receptor antagonist, 8-cyclopentyltheophylline (200 nM), prevented the neuronal cell death caused by exposure of rat cultured cerebellar granule neurons to fragment 25-35 of beta-amyloid protein (25 micro M for 48 h), that by itself caused a near three-fold increase of propidium iodide-labeled cells. This constitutes the first in vitro evidence to suggest that adenosine A(2A) receptors may be the molecular target responsible for the observed beneficial effects of caffeine consumption in the development of Alzheimer's disease.

Chronic treatment with caffeine blunts the hyperlocomotor but not cognitive effects of the N-methyl-D-aspartate receptor antagonist MK-801 in mice.

Rationale: Administration of N-methyl- d-aspartate (NMDA) receptor antagonists produce hyperlocomotion and cognitive deficits in rodents. Activation of NMDA receptors promotes adenosine release, and adenosine agonists prevent central effects of NMDA receptor antagonists. We hypothesized that if NMDA receptor antagonists require adenosine to produce behavioral effects, mice tolerant to the adenosine receptor antagonist caffeine would have a diminished response to NMDA receptor antagonists.

Decreased hyperlocomotion induced by MK-801, but not amphetamine and caffeine in mice lacking cellular prion protein (PrP(C)).

The cellular prion protein (PrP(C)) has been involved in several neurodegenerative disorders however it has been proposed that it is also be implicated in psychotic disorders. We investigated the effect of three psychotropic drugs in locomotor activity of PrP(C) knockout (Prnp(O/O)) and wild-type mice. The NMDA receptor channel blocker MK-801 (0.