There is substantial evidence that drug-paired cues become associated with drug effects. From a Pavlovian perspective, these cues act as conditioned stimuli and elicit conditioned compensatory responses that contribute to drug tolerance. Here we report two experiments with rats in which we studied the extinction of the associative tolerance to the ataxic effect of ethanol. Experiment 1 evaluate...

The development of tolerance to a drug at the level of the neuron reflects a homeostatic mechanism by which neurons respond to perturbations of their function by external stimuli. Acute functional tolerance (AFT) to ethanol is a fast compensatory response that develops within a single drug session and normalizes neuronal function despite the continued presence of the drug. We performed a geneti...

Analgesic tolerance to opioids has been described in both experimental and clinical conditions and may limit the clinical utility of these drugs. We have previously shown that systemic gabapentin (GBP), a non-opioid drug, prevents and reverses tolerance to systemic morphine in the rat. In this study, we investigated the effect of intrathecal GBP on spinal morphine tolerance. Studied rats were g...

Caffeine is the psychostimulant substance consumed in greatest quantities in the world. The repeated administration of psychostimulants can either decrease or increase the drug effect, inducing tolerance or sensitization, respectively, depending on administration procedure. Not only the dose and regimen, but also the environment where drug is administered, seem to modulate the changes in locomo...

Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters that is dynamically maintained within a wide ...

Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing

In recent experiments on isogenetic cancer cell lines, it was observed that exposure to high doses of anticancer drugs can induce the emergence of a subpopulation of weakly proliferative and drug-tolerant cells, which display markers associated with stem cell-like cancer cells. After a period of time, some of the surviving cells were observed to change their phenotype to resume normal prolifera...

Late-stage tritiation with high selectivity, isotopic purity and functional-group tolerance is important for the radiolabelling of drug candidates or bioactive compounds. Now, a broadly applicable protocol using aryl thianthrenium salts allows complex molecules by hydrogenolysis via an intermediate cationic palladium complex.

background:  a great number of premature neonates do not tolerate sufficient milk during the early neonatal period.   objective: to evaluate the effect of oral erythromycin on enhancement of feeding tolerance in preterm newborns.   methods: sixty preterm neonates intolerant to milk of >75 ml/kg/day during 5 days after the start of feedings, were randomized into a treatment and a control groups....