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Conflict procedures can be used to study the receptor mechanisms underlying the anxiolytic effects of benzodiazepines and other GABA(A) receptor modulators. In the present study, we first determined the efficacy and binding affinity of the benzodiazepine diazepam and recently synthesized GABA(A) receptor modulators JY-XHe-053, XHe-II-053, HZ-166,(More)
RATIONALE The stress-induced hyperthermia (SIH) model is an anxiety model that uses the transient rise in body temperature in response to acute stress. Benzodiazepines produce anxiolytic as well as sedative side effects through nonselective binding to GABA(A) receptor subunits. The GABA(A) receptor alpha(1) subunit is associated with sedation, whereas the(More)
Benzodiazepine pharmacology has led to greater insight into the neural mechanisms underlying learning and anxiety. The synthesis of new compounds capable of modulating responses produced by these receptors has been made possible by the development of an isoform model of the GABA(A)/benzodiazepine receptor complex. In the current experiment, rats were(More)
Recent research using genetically modified mice has pointed to the specific contribution of individual receptor subtypes to the various effects of benzodiazepines. The aim of this study was to examine the relative significance of alpha(1)-containing GABA(A) receptors in the effects of modulators at the benzodiazepine site in the elevated plus-maze (EPM)(More)
The ethyl ester of beta-carboline-3-carboxylic acid has a high affinity for benzodiazepine receptors in the brain. In the rhesus monkey this substance produces an acute behavioral syndrome characterized by dramatic elevations in heart rate, blood pressure, plasma cortisol, and catecholamines. The effects are blocked by benzodiazepines and the specific(More)
The radiochemical synthesis and pharmacological properties are described of [3H]RY 80 (ethyl-8-acetylene-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][1, 4]benzodiazepine-3-carboxylate, [ethyl-3H]). This compound is one of a series of 8-substituted imidazobenzodiazepines that exhibits both high affinity and selectivity for gamma-aminobutyric acid (GABA)A(More)
The clinical use of benzodiazepines (BZs) is hampered by sedation and cognitive deterioration. Although genetic and pharmacological studies suggest that alpha1- and alpha5-containing GABA(A) receptors mediate and/or modulate these effects, their molecular substrate is not fully elucidated. By the use of two selective ligands: the alpha1-subunit(More)
The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, ip) were observed for compounds 2-4 in(More)
RATIONALE Positive modulators of the benzodiazepine/GABA(A) receptor complex can heighten aggressive behavior; the GABA(A)/alpha(1) subunit may play a critical role in benzodiazepine-modulated aggressive behavior. OBJECTIVE The carboline derivatives, beta-CCt and 3-PBC, antagonists with preferential action at the GABA(A) receptors with alpha(1) subunits,(More)
We investigated the potential role of the alpha1-containing GABA(A) receptor in regulating the reinforcing properties of alcohol. To accomplish this, we developed 3-propoxy-beta-carboline hydrochloride (3-PBC), a mixed agonist-antagonist benzodiazepine site ligand with binding selectivity at the alpha1 receptor. We then tested the capacity of 3-PBC to block(More)