1. Psychology/Biology 3506 Neuropharmacology
Dr. David R. Brodbeck

2. Introduction What is a drug? Some things are also poisons
Well, we all know what it means…
That ain’t 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 don’t need a definition

3. 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.

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

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

6. 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

7. Dose Response Curves
Effect of morphine and morphine + naloxone on activity (left) and nosepoke (right) (Criswell, 1987)

8. 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

9. 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

10. 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….

11. Key Terms, Continued Agonists Antagonists Additive effects
Naloxone and opiates for example
Additive effects
Superadditive effects
Sleeping pills and martinis

12. Routes of Administration
If you are injecting, you need a vehicle
Saline
Subcutaneous
Slowest absorption
Intramuscular
Intraperitoneal
Fastest absorption of these three
Intravenous
intraventricular

13. 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

14. 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

15. What affects metabolism?
Age
Sex
Species
Enzyme induction
Enzyme depression
Putting absorption and excretion together, you get the time course of the drug

16. 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 shorter

17. So, there’s 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

18. 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
Followed up in 1978 with a classic paper

19. 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

20. Common Dependent Variables
Arousal level (use EEG)
Perceptual stuff
Flicker fusion
Thresholds
Timing
Cognitive stuff
Memory
vigilance

21. More Measures Motor tasks Non humans too Pursuit rotor Tapping rate
Timing
Learning and memory
Avoidance
Paw lick test

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