Behavioral Neuroscience -  Neuropharmacology

  • Neuropharmacology   * the study of how substances affect our nervous system and behavior     * one of the main areas of neuroscience research today   * usually starts with animal research, once safety is established moves to human clinical studies   * often (but not always) involves comparing active substances to a placebo (saline solution)     * may use “active” placebo and may use double-blind research design
  • Basic terms   * Agonist --- increases NT activity   * Antagonist --- decreases NT activity   * Placebo --- an inert substance that is given to an organism instead of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug     * sometimes creates same effect as the drug

Research terms

  • Half-life --- time it takes 1/2 of the drug to leave the body   * used as a safety and maintenance factor   * must examine drug “metabolites” as well as active ingredients   * Drug metabolism: the process by which the body breaks down and converts medication into altered chemical substances   * can be active or inactive     * may not cause desired effect but affect other things; active = produce effect, inactive don’t   * Elimination of a drug characterized by more than one half-lif every time half is eliminated = half-life   * Time required for a drug concentration to reach steady state is determined by half-life   * in most clinical situations, the attainment of steady state can be assumed after 3-5 half-lives   * When the drug concentration is around 5% it is said to be negligible, therefore around 4 or 5 half-lives must elapse until the drug is eliminated   * Time for drug “negligibility” = half-live * 5
  • Dose-response curve   * a graph of the relationship between drug doses and the effects   * attempts to find effective and safe dose of drug   * can be used to plot the results of many kinds of experiments; X-axis usually drug/hormone concentration, Y-axis plots response (can be almost anything) \n * have to do a different curve for each of the effects of drug including side-effects   * the specific measurement (DV) will be defined b/c pharmacological agents can have multiple effects   * plots increasing drug dose (usually on a logarithmic scale) against increasing strength of the response being studied   * the dose at which the drug shows half of its maximal effect is termed the effective dose 50% (ED50) ED50 = the dose at which 50% of the population sees an effect   * Therapeutic window--- many drugs only work at specific doses; high and low often have little effect   * Nonmonotonic DRC --- a DRC that is normal up to a point but then reverses and the measured response begins to decrease with larger doses
  • Dose-response functions   * Minimum effective dose (ED50) --- lowest dose to produce desired effect in 50 % of clinical subjects   * Median Toxic dose (TD50) --- dose which produces the first signs of toxicity in 50% population     * high build-up in blood   * Threshold dose --- smallest dose to produce detectable change   * change must be defined by therapeutic effect   * We can assess the relative potency of two drugs by comparing their ED50 values   * Maximum response (max dose) --- the greatest degree of response that can be achieved with a specific drug     * usually there is a plateau effect past which further dose do not increase effect     * sometimes higher doses decrease effect (like amphetamines) because other effects begin to interfere with desired effect     * We can compare drug efficacies by evaluating maximal responses, rather than doses     * Partial agonist/antagonist - a drug of only moderate efficacy   * Therapeutic index (TI) --- the separation between the effective dose and a toxic one     * Safe index - ratio between TD50/ED50     * TI = 100x safe (over-the-counter), TI =10x hazardous     * becomes an issue with uncontrolled recreational use---tolerance to recreational effect occurs very quickly
  • Clinical efficacy---refers to the degree to which a drug is able to induce a given effect   * related to maximal response   * DRC can allow the comparison of difference drugs
  • Potency-- the amount of a drug needed to produce a desired effect   * lower the needed dose, more potent

Drug interactions

  • Affinity - capacity of a compound (drug) to maintain contact or be bound to a receptor
  • binding affinity = the degree of chemical attraction between a ligand and a receptor   * a drug with a high affinity for its receptor will be effective at very low doses   * when two substances are being taken, one with the most affinity will have greater effect   * penicillin and alcohol

Tolerance/Dependency

  • Tolerance - when there’s a decreased susceptibility or increase in amount of drug being taken needed   * represented by a rightward shift in the dose response curve   * has a physiological and psychological component
  • Factors   * Metabolic tolerance --- organ systems become more effective at eliminating the drug   * Elevation in Hepatic Microsomal Enzyme (HME) - reduces drug to metabolites so they become ineffective and easier to eliminate     * ‘hepatic’ = liver     * creates inactive and easier-to-eliminate metabolites     * with repeated use of the brain creates more HMEs     * associated with cross-tolerance to related substances       * tolerance to once drug gives pre-existing tolerance to another (ex. surgical, analgesics, and narcotics)     * creates dangerous interactions between drugs that share the same HMEs---sedatives and alcohol       * biotransformation produces active metabolites that may produce side effects   * Functional tolerance: target tissue may show altered sensitivity to the drug   * up and down-regulation of receptors   * with repeated drug use nervous sys can respond by altering the density of post-synaptic receptors   * increase density = up-regulation, antagonist   * lower density= down regulation; agonist
  • Drug dependent
  • Physical dependency: when

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