The objective of this study was the construction of a pharmacokinetic-pharmacodynamic model to describe the effects of chlorprothixene on prolactin secretion and the time-dependent alterations in the concentration-effect relationship due to tolerance development. Prolactin and chlorprothixene serum concentrations were determined in eight healthy men for up to 72 h after the intravenous and oral...

OBJECTIVE The mechanism of action of fatty acid synthase (FASN) in drug tolerance of breast cancer cells with epithelial-mesenchymal transition (EMT) features was investigated. METHODS The breast cancer cell line MCF-7-MEK5 with stably occurring EMT and tumour necrosis factor-α (TNF-α) tolerance was used as the experimental model, whereas MCF-7 acted as the control. Tumour cells were implante...

Alcohol addiction is a disease that includes a diverse set of phenotypes. Functional alcohol tolerance is an adaptation to the effects of alcohol that restores neuronal homeostatic balance while the drug is present. When the drug is suddenly withheld, these adaptations unbalance the nervous system and are thought to be the origin of some withdrawal symptoms. Withdrawal symptoms, which can be a ...

Cues associated with familiar alcoholic drinks such as beer may, through repeated association with the unconditioned stimulus properties of alcohol, acquire the status of classically conditioned stimuli. It has been proposed that such drug-related conditioned stimuli mediate drug tolerance. Thus, the aim of the present experiment was to test this proposition on cognitive, subjective, and psycho...

Background and Objective: Today, opioids are used to control and relieve acute and chronic pain. However, the incidence of both tolerance and dependence phenomena for these drugs is a major problem. So, in this study, the combination effect of haloperidol and methadone on the acquisition and expression of morphine dependence and tolerance was examined.    Materials and Methods: Ninety-eight mic...

Opiate analgesia, tolerance, and addiction are mediated by drug-induced activation of the mu opioid receptor. A fundamental question in addiction biology is why exogenous opiate drugs have a high liability for inducing tolerance and addiction while native ligands do not. Studies indicate that highly addictive opiate drugs such as morphine are deficient in their ability to induce the desensitiza...

N Engl J Med 2003;349:975-86. Copyright © 2003 Massachusetts Medical Society. rug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences. Addictive substances induce pleasant states (euphoria in the initiation phase) or relieve distress. Continued use induces adaptive changes in the central nervous syst...