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Large numbers of neuritic plaques surrounded by reactive astrocytes are characteristic of Alzheimer's disease (AD). There is a large body of research supporting a causal role for the amyloid beta peptide (Abeta), a main constituent of these plaques, in the neuropathology of AD. Several hypotheses have been proposed to explain the toxicity of Abeta including(More)
Certain neuroleptic drugs, such as spiperone and (+) butaclamol, can discriminate between two populations of [3H]5-hydroxytryptamine ([3H]5-HT) binding sites in rat brain. The butyrophenone neuroleptic spiperone shows the greatest selectivity for these two binding sites, having at least a 3000-fold difference between its dissociation constants (2-12 nM(More)
beta-Amyloid (A beta), the central constituent of senile plaques in Alzheimer's disease (AD) brains, was shown by us recently to generate free radicals in an oxygen dependent mechanism. A beta-derived free radicals were detected directly using electron paramagnetic resonance (EPR) spin trapping techniques employing the spin trap(More)
BACKGROUND We recently reported that the sodium salt of acamprosate (Na-acamprosate) demonstrates the characteristics of an antagonist at metabotropic glutamate type 5 receptors (mGluR5s) rather than at N-methyl-d-aspartate receptors (NMDARs). Because mGluR5s are able to enhance the function of NMDARs, this interplay may be involved in the dysregulation of(More)
BACKGROUND Several reported effects of acamprosate within the glutamatergic system could result from interactions with metabotropic glutamate receptors (mGluRs). The following experiments were performed to determine whether acamprosate could compete with trnas-ACPD (+/--1-aminocyclopentane-trans-1,3-dicarboxylic acid, an equimolecular mixture of 1S, 3R and(More)
The purpose of this review is to summarize much of the work on the inhibition of the astroglial glutamate transporter in relation to excitotoxic neurodegeneration, in particular, inhibition of uptake by the beta-amyloid peptide (A beta) found in the Alzheimer's disease (AD) brain. There is evidence for oxidative stress in the AD brain, and A beta has been(More)
Antinociceptive activity of intraventricularly administered acetylcholine was quantitated in mice by the tail-flick and phenylquinone tests. Acetylcholine was administered intraventricularly under light ether anesthesia in a 5 mul volume of sterile saline and mice were retested 10 minutes after the operation. A dose-response curve was established for(More)
Neurotransmitter receptor plasticity is an important part of the compensatory processes by which the central nervous system adapts to pathological insult, long-term exposure to drugs or neuronal loss with advanced age. Receptor plasticity can be manifest as changes in the number of receptors (i.e., up- or down-regulation), changes in expression of mRNA for(More)
Central cholinergic pathways modulate both the perception of excessive motion stimuli and the expression of motion sickness symptoms, such as nausea and vomiting. Specific brainstem areas which mediate motion-induced emesis include the area postrema (AP), vagal nuclear complex (VNC), reticular formation (RF) at the site of the vomiting center, and the(More)
BACKGROUND Several reports demonstrate that withdrawal from long-term ethanol exposure is associated with significant central nervous system neurotoxicity, produced at least in part by increased activity of N-methyl-d-aspartate receptors (NMDARs). Recent evidence suggests that elevations in the synthesis and release of the polyamines spermidine and(More)