Repeated administration of many psychoactive drugs results in diminished effectiveness of the drug, a phenomenon named tolerance. A great deal of research has shown that associative learning contributes to tolerance (see Siegel & Ramos, 2002, for a recent review). Siegel (1975) proposed a model of tolerance in which drug administration was seen as an example of Pavlovian or classical conditioni...

Heroin overdose deaths in the Unites States more than tripled from 2010 to 2014, reaching almost 11,000 per year. Despite the use of the term “overdose,” many of these victims died after self-administering an amount of opiate that would not be expected to be fatal for these drug-experienced, and drug-tolerant, individuals. Various explanations of this overdose mystery have been proposed. I desc...

Basic research concerning drug tolerance and withdrawal may inform clinical practice, and vice versa. Three areas that integrate the work of the laboratory and the clinic are discussed: (a) drug overdose, (b) cue exposure treatment of addiction, and (c) pharmacological treatment of withdrawal symptoms. The areas are related in that they indicate the contribution of drug-paired cues to the effec...

Drug tolerance in bacteria is widely believed to be due to metabolic changes that accompany growth arrest. A study in this issue of Cell reveals a drug tolerance mechanism in replicating mycobacteria that is induced by residence in macrophages and depends on drug efflux.

Drug tolerance and withdrawal are insidious responses to drugs of abuse; the first increases drug consumption while the second punishes abstention. Drosophila generate functional tolerance to benzyl alcohol sedation by increasing neural expression of the slo BK-type Ca(2+) activated K(+) channel gene. After drug clearance this change produces a withdrawal phenotype-increased seizure susceptibil...

Several papers have documented the disproportionate representation of African Americans in school discipline and incarceration settings as a result of zero tolerance policies. In 2009, a federal study of the Chicago Public School system found African American boys represented 23 percent of the school age population, 44 percent of students who were suspended, and 61 percent of students who were ...