Psychology 3506 Neuropharmacology

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Psychology 3506Neuropharmacology

• Dr. David R. Brodbeck

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Introduction

• What is a drug?
• Well, we all know what it means
• That aint good enough, we need some sort of
  definition
• Alters physiology, but is not food..
• Vitamin C?
• Some things are also poisons
• Gasoline, mugwart..
• Perhaps we dont need a definition

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Still.

• What if you take it not to treat anything or to
  get high
• Coke
• Coffee
• Beer
• Frankly, an intuitive definition will have to do.

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Names

• Chemical Names
• 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benz
  odiazepin-2-one.
• How very helpful.
• Generic Names
• diazepam
• flouexitine
• Trade Names
• Valium
• Prozac

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Dosages

• Different dosage sizes will have different
  effects on different people, animals.
• Especially if they weigh different amounts
• Standardize it
• mg/kg

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Dose Response Curves

• Pick some variable for a response
• Plot response as a function of dose
• One drink and I am relaxed
• 4 drinks and I am tipsy
• 8 drinks and I am relaxed again.
• This shape is very common in DRCs

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Dose Response Curves

• Effect of morphine and morphine naloxone on
  activity (left) and nosepoke (right) (Criswell,
  1987)

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Describing Effectiveness

• ED50 and LD50
• Effective dose for 50 percent of the population
• subjective
• Lethal dose for 50 of the population
• Therapeutic Index (TI)
• TI LD50 / ED50
• Higher the index, the safer the drug

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Potency and Effectiveness or Efficacy

• Find the ED50 for both drugs
• The one with the lower ED50 is more potent
• Efficacy is about the maximum amount of effect
  the drug will have
• Morphine vs. aspirin

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Some other key terms

• Primary effects or main effects vs. side effects
• Depends on your point of view
• If you are taking morphine to deal with pain, the
  main effect is the analgesia and the (albeit fun)
  side effect is being high
• If you are taking it because you want to groove
  to Quicksilver Messenger Service.

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Key Terms, Continued

• Agonists
• Antagonists
• Naloxone and opiates for example
• Additive effects
• Superadditive effects
• Sleeping pills and martinis

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Routes of Administration

• If you are injecting, you need a vehicle
• Saline
• Subcutaneous
• Slowest absorption
• Intramuscular
• Intraperitoneal
• Fastest absorption
• Intravenous
• intraventricular

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Routes

• Get into bloodstream via diffusion
• (except IV injections obviously)
• Inhalation works the same way
• Gasses or solids
• Orally, depends on lipid solubility
• More soluble the easier the absorption
• Ionized molecules are not absorbed
• Rate is constant

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Distribution and Metabolism

• Once absorbed, the drug has to get past the blood
  brain barrier
• Get across the membrane through passive or active
  transport
• Protein binding stops some
• Taken out of blood stream by kidneys, liver
• Measured in half life

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What affects metabolism?

• Age
• Sex
• Species
• Enzyme induction
• Enzyme depression
• Putting absorption and excretion together, you
  get the time course of the drug

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Therapeutic window

• You want to maintain enough of the drug in the
  system
• Easy if the drug has a long time course
• Harder if the time course is longer

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So, theres the pharmacology, what about the
behaviour?

• In behavioural pharmacology we use dose as the
  Independent variable and response (behaviour) ad
  the dependent variable
• Need a control group or control condiiton
• Between subjects designs
• Within subjects designs
• Statistical tests are done
• Placebo controls are VERY IMPORTANT

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Importance of placebo controls

• Levine, Gordon and Fields (1977)
• 2 groups, one given real analgesic, other given
  placebo
• Both report analgesia!
• Naloxone given
• Only return of pain in analgesia group

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I bet you could teach a course on research
methods.

• Co relational research is also important
• CORRELATION IS NOT CAUSATION
• Science is not done in a vacuum
• Unstructured observation is as useful as
  champagne in the Leafs dressing room
• Can lead to ideas though
• Systematic introspection is OK
• Questionnaires like the MPQ

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Common Dependent Variables

• Arousal level (use EEG)
• Perceptual stuff
• Flicker fusion
• Thresholds
• Timing
• Cognitive stuff
• Memory
• vigilance

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More Measures

• Motor tasks
• Pursuit rotor
• Tapping rate
• Non humans too
• Timing
• Learning and memory
• Avoidance
• Paw lick test

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Conditioning

• Drug effects can be conditioned
• But, UR ltgt CR (not always anyway)
• If drug affects PNS, you get the opposite
  effect!!
• Behavioural Tolerance
• Campbell and Sieden (1973)
• Amphetamine and DRL