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
  • 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)
  • 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