Furthermore, we show that receptors formed by alpha 4 beta 3 subunits alone also show high GABA sensitivity and that saturating GABA responses of alpha 4 beta 3 receptors are increased to the same extent by etomidate, propofol, and THDOC as are alpha 4 beta 3 delta receptors. Therefore, both alpha 4 beta 3 and alpha 4 beta 3 delta receptors show low GABA efficacy, and GABA is also a partial agonist on certain binary alpha beta receptor subtypes. Increasing GABA efficacy on alpha 4/6 beta Z-DEVD-FMK datasheet 3 delta and alpha 4 beta 3 receptors is likely to make an important contribution to the anesthetic effects of etomidate, propofol

and the neurosteroid THDOC. (C) 2008 Elsevier Ltd. All rights reserved.”
“Repeated intermittent exposure to psychostimulants can lead to long-lasting sensitization CDK inhibitor of the drugs’ behavioral and biochemical effects. Such findings have figured importantly in recent theories of drug addiction

proposing that sensitized nucleus accumbens (NAcc) dopamine (DA) overflow in particular acts in concert with other alterations in the neurochemistry of this nucleus to promote drug seeking and self-administration. Yet, experiments in rodents, non-human primates and humans have not always detected behavioral or biochemical sensitization following drug exposure, bringing into doubt the utility of this In an effort to reconcile apparent discrepancies in the literature, this review assesses conditions model. that might affect the expression of sensitization during testing. Specifically, the role played by conditioned cues is reviewed. A number of reports strongly support a potent and critical role for conditioned stimuli in the expression of sensitization. Findings suggest that stimuli associated either with the presence or absence of drug can respectively facilitate or inhibit sensitized responding. It is concluded that the presence or

absence of such stimuli during testing for sensitization in animal and human studies could significantly affect the results Selleck C188-9 obtained. It is necessary to consider this possibility especially when interpreting the results of studies that fail to observe sensitized responding. (c) 2008 Elsevier Ltd. All rights reserved.”
“Penicillin, an open-channel blocker of GABA(A) receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and context-dependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABAA receptors expressed in HEK293T cells.