The effects of benzodiazepine inverse agonists on the long-term potentiation of synaptic transmission in hippocampal slices of the guinea pig were examined using an extracellular recording technique. Benzodiazepine inverse agonists, beta-carboline-3-carboxylate (beta-CCE), 2-phenylpyrazolo [4,3-c]quinolin-3(5H)-one (CGS-8216) and 2-[5-methylthien-3-yl]-2,5-dihydro-3H-pyrazolo [4,3-c]quinolin-3-...

Despite decades of basic and clinical research, our understanding of how benzodiazepines tend to lose their efficacy over time (tolerance) is at least incomplete. In appears that tolerance develops relatively quickly for the sedative and anticonvulsant actions of benzodiazepines, whereas tolerance to anxiolytic and amnesic effects probably does not develop at all. In light of this evidence, we ...

The distribution and mobility of GABA/benzodiazepine receptors has been examined on living nerve cells by fluorescence digital imaging and fluorescence photobleach recovery with 2 novel fluorescent derivatives of the benzodiazepines Ro7-1986 and 1012S. These fluorescent derivatives retain their high affinity for the GABA/benzodiazepine receptor complex with Ks of 79 and 85 nM, respectively. Dig...

The presence of specific benzodiazepine binding sites in the hearts of dogs and human beings was demonstrated in vivo by a noninvasive method, positron emission tomography (PET). An antagonist of the peripheral-type benzodiazepine binding site, PK 1 1 195, was labeled with carbon1 1, a short-lived positron emitter. When injected at high specific activity, 1C-PK l 1195 was concentrated in the my...

Neuroinflammation is a major component of several neurodegenerative disorders such as Alzheimer's disease, HIV-associated dementia, Multiple sclerosis and Parkinson's disease. Although the primary pathology underlying each of these diseases is vastly different, neuroinflammation, consisting of chronic activation of brain macrophages, is a significant factor that contributes to neuronal damage i...

Delivery of cholesterol to inner mitochondrial membranes is rate-limiting for steroidogenesis in the zona fasciculata of adrenal cortex. A protein that stimulates this process was isolated to homogeneity from bovine adrenal tissue. This protein's primary structure has been determined in its entirety by a combination of automated Edman microsequencing, fast-atom bombardment mass spectrometry (FA...

Four sesquiterpenes, beta-selinene, isocurcumenol, nootkatone and aristolone and one triterpene, oleanolic acid were isolated from the ethylacetate fraction of the rhizomes of Cyperus rotundus and tested for their ability to modulate gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor function by radioligand binding assays using rat cerebrocortical membranes. Among these compounds, only i...

For over 20 years, numerous investigations have focused on elucidating the function of the peripheral benzodiazepine receptor (PBR). This relatively small protein (18kDa) arouses great interest because of its association with numerous biological functions, including the regulation of cellular proliferation, immunomodulation, porphyrin transport and heme biosynthesis, anion transport, regulation...

Chronic benzodiazepine treatment can produce tolerance and changes in g-aminobutyric acid (GABA)A receptors. To study the effect of treatment on a selected population of receptors, assays were performed using [H]RY-80, which is selective for GABAA receptors with an a5 subunit. Rats were given a flurazepam treatment known to produce tolerance and down-regulation of benzodiazepine binding, or a d...

One week oral flurazepam (FZP) administration in rats results in reduced GABA(A) receptor-mediated synaptic transmission in CA1 pyramidal neurons associated with benzodiazepine tolerance in vivo and in vitro. Since voltage-gated calcium channel (VGCC) current density is enhanced twofold during chronic FZP treatment, the role of L-type VGCCs in regulating benzodiazepine-induced changes in CA1 ne...