Which type of tolerance involves nerve cells becoming less sensitive to a drug's effects over time?

Pharmacodynamic tolerance refers to the process by which nerve cells and receptor sites in the brain become less sensitive to a drug's effects over time. This type of tolerance occurs at the cellular level, where prolonged exposure to a substance leads to adaptations such as receptor desensitization or downregulation. As a result, a person may require higher doses of the substance to achieve the same effect that was initially experienced, as the body's response diminishes due to the decreased sensitivity of nerve cells.

This phenomenon contrasts with metabolic tolerance, which involves the liver becoming more efficient at metabolizing a substance, leading to a reduction in its concentration in the body. Behavioral tolerance is related to the individual's ability to adjust their behaviors to compensate for the effects of the drug, while cross-tolerance occurs when tolerance to one drug results in a decreased response to a pharmacologically similar drug due to shared biological mechanisms. All these concepts are important in understanding how tolerance can develop in individuals who use substances over time, but pharmacodynamic tolerance specifically highlights the changes in nerve cell sensitivity that occur directly as a consequence of drug exposure.