Tolerance to drugs that affect neural activity is mediated, in part, by adaptive mechanisms that attempt to restore normal neural excitability. Changes in the expression of ion channel genes are thought to play an important role in these neural adaptations. The slo gene encodes the pore-forming subunit of BK-type Ca(2+)-activated K(+) channels, which regulate many aspects of neural activity. Gi...

drug when nearing exhaustion which would lead to a decline in the response to the drug. Most likely the development of drug tolerance to beta, agonists involves more than one mechanism. The workshop was fruitful in amunulating further evidence that drug tolerance to beta, agonists does develop. It is clear that further studies are needed to define the clinical sigdicance of drug tolerance, the ...

Introduction: Topiramate is an anti-convulsant drug, which produces its effects via glutamate metabotropic receptors inhibition and/or GABA receptor excitation. In the present study, attempts were made to investigate the effects of topiramate on the tolerance to morphine-induced analgesia activity in male NMRI mice (20-30 g). Methods: Hot plate method was chosen for the study. First of all t...

Tolerance is usually defined as a reduction in the effects for the drug in question such that a higher dose (or blood concentration) of the drug is required to produce the same degree of effects as seen previously in the drug-naive individual. Tolerance is a complex phenomenon that develops as a result of adaptation of the organism to the presence of drugs in certain circumstances and can devel...

To the Editor: Corti et al1 recently reported that habitual coffee drinkers display different degrees of caffeine tolerance, depending on the route of caffeine administration. Although the participants did not display elevated systolic blood pressure after consumption of caffeinated coffee, they did after intravenous caffeine administration. In both conditions, the amount of caffeine administer...

Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced tolerance to rifampicin and intracellular growth. In this study, we infected the human macrophage-like cell line THP-1 with drug-sensitive and drug-resistant M. tuberculosis strains and found that ...

The preceding paper presented a model of drug tolerance and dependence. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considere...

There is considerable evidence that drug-paired cues become associated with drug effects. It has been hypothesized that these cues act as Pavlovian conditional stimuli (CSs), and elicit conditional compensatory responses that contribute to tolerance. On the basis of a conditioning analysis of tolerance, we would expect that it should be possible to establish drug-paired cues as occasion setters...