Psychology 3506Psychology 3506NeuropharmacologyNeuropharmacology

Dr. David R. BrodbeckDr. David R. Brodbeck

IntroductionIntroduction

What is a drug?What is a drug?– Well, we all Well, we all knowknow what it means… what it means…– That ain’t good enough, we need some sort of That ain’t good enough, we need some sort of

definitiondefinition– Alters physiology, but is not food…..Alters physiology, but is not food…..

Vitamin C?Vitamin C?

Some things are also poisonsSome things are also poisons– Gasoline, mugwart..Gasoline, mugwart..

Perhaps we don’t need a definitionPerhaps we don’t need a definition

Still….Still….

What if you take it not to treat anything or What if you take it not to treat anything or to get highto get high– CokeCoke– CoffeeCoffee– BeerBeer

Frankly, an intuitive definition will have to Frankly, an intuitive definition will have to do.do.

NamesNames

Chemical NamesChemical Names– 7-chloro-1,3-dihydro-1-7-chloro-1,3-dihydro-1-

methyl-5-phenyl-2H-1,4-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.benzodiazepin-2-one.

– How very helpful….How very helpful….

Generic NamesGeneric Names– diazepamdiazepam– flouexitineflouexitine

Trade NamesTrade Names– ValiumValium– ProzacProzac

DosagesDosages

Different dosage sizes will have different Different dosage sizes will have different effects on different people, animals. effects on different people, animals.

Especially if they weigh different amountsEspecially if they weigh different amounts

Standardize itStandardize it

mg/kgmg/kg

Dose Response CurvesDose Response Curves

Pick some variable for a responsePick some variable for a response

Plot response as a function of dosePlot response as a function of dose

One drink and I am relaxedOne drink and I am relaxed

4 drinks and I am tipsy4 drinks and I am tipsy

8 drinks and I am ‘relaxed’ again.8 drinks and I am ‘relaxed’ again.

This shape is very common in DRCsThis shape is very common in DRCs

Dose Response CurvesDose Response Curves

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

Describing EffectivenessDescribing Effectiveness

EDED5050 and LD and LD5050

Effective dose for 50 percent of the Effective dose for 50 percent of the populationpopulation– subjectivesubjective

Lethal dose for 50% of the populationLethal dose for 50% of the population

Therapeutic Index (TI)Therapeutic Index (TI)– TI = LDTI = LD50 50 / ED/ ED5050

– Higher the index, the safer the drugHigher the index, the safer the drug

Potency and Effectiveness or Potency and Effectiveness or EfficacyEfficacy

Find the EDFind the ED5050 for both drugs for both drugs

The one with the lower EDThe one with the lower ED5050 is more is more

potentpotent

Efficacy is about the maximum amount of Efficacy is about the maximum amount of effect the drug will haveeffect the drug will have

Morphine vs. aspirinMorphine vs. aspirin

Some other key termsSome other key terms

Primary effects or main effects vs. side Primary effects or main effects vs. side effectseffects– Depends on your point of viewDepends on your point of view– If you are taking morphine to deal with pain, If you are taking morphine to deal with pain,

the main effect is the analgesia and the (albeit the main effect is the analgesia and the (albeit fun) side effect is being highfun) side effect is being high

– If you are taking it because you want to If you are taking it because you want to groove to Quicksilver Messenger Service….groove to Quicksilver Messenger Service….

Key Terms, ContinuedKey Terms, Continued

AgonistsAgonists

AntagonistsAntagonists– Naloxone and opiates for exampleNaloxone and opiates for example

Additive effectsAdditive effects

Superadditive effectsSuperadditive effects– Sleeping pills and martinisSleeping pills and martinis

Routes of AdministrationRoutes of Administration

If you are injecting, you need a vehicleIf you are injecting, you need a vehicle– SalineSaline

SubcutaneousSubcutaneous– Slowest absorptionSlowest absorption

IntramuscularIntramuscular

IntraperitonealIntraperitoneal– Fastest absorptionFastest absorption

IntravenousIntravenous

intraventricularintraventricular

Routes…Routes…

Get into bloodstream via diffusionGet into bloodstream via diffusion– (except IV injections obviously)(except IV injections obviously)

Inhalation works the same wayInhalation works the same way– Gasses or solidsGasses or solids

Orally, depends on lipid solubilityOrally, depends on lipid solubility– More soluble the easier the absorptionMore soluble the easier the absorption– Ionized molecules are not absorbedIonized molecules are not absorbed– Rate is constantRate is constant

Distribution and MetabolismDistribution and Metabolism

Once absorbed, the drug has to get past Once absorbed, the drug has to get past the blood brain barrierthe blood brain barrier

Get across the membrane through passive Get across the membrane through passive or active transportor active transport

Protein binding stops someProtein binding stops some

Taken out of blood stream by kidneys, Taken out of blood stream by kidneys, liverliver– Measured in half lifeMeasured in half life

What affects metabolism?What affects metabolism?

AgeAgeSexSexSpeciesSpeciesEnzyme inductionEnzyme inductionEnzyme depressionEnzyme depressionPutting absorption Putting absorption and excretion and excretion together, you get the together, you get the time coursetime course of the of the drugdrug

Therapeutic windowTherapeutic window

You want to maintain enough of the drug You want to maintain enough of the drug in the systemin the system

Easy if the drug has a long time courseEasy if the drug has a long time course

Harder if the time course is longerHarder if the time course is longer

So, there’s the pharmacology, what So, there’s the pharmacology, what about the behaviour?about the behaviour?

In behavioural pharmacology we use dose In behavioural pharmacology we use dose as the as the Independent variableIndependent variable and response and response (behaviour) ad the (behaviour) ad the dependent variabledependent variable

Need a control group or control condiitonNeed a control group or control condiiton– Between subjects designsBetween subjects designs– Within subjects designsWithin subjects designs

Statistical tests are doneStatistical tests are done

Placebo controls are VERY IMPORTANTPlacebo controls are VERY IMPORTANT

Importance of placebo controlsImportance of placebo controls

Levine, Gordon and Fields (1977)Levine, Gordon and Fields (1977)– 2 groups, one given real analgesic, other 2 groups, one given real analgesic, other

given placebogiven placebo– Both report analgesia!Both report analgesia!– Naloxone givenNaloxone given– Only return of pain in analgesia groupOnly return of pain in analgesia group

I bet you could teach a course on I bet you could teach a course on research methods….research methods….

Co relational research is also importantCo relational research is also important

CORRELATION IS NOT CAUSATIONCORRELATION IS NOT CAUSATION

Science is not done in a vacuumScience is not done in a vacuum

Unstructured observation is as useful as Unstructured observation is as useful as champagne in the Leafs dressing roomchampagne in the Leafs dressing room– Can lead to ideas thoughCan lead to ideas though

Systematic introspection is OKSystematic introspection is OK– Questionnaires like the MPQQuestionnaires like the MPQ

Common Dependent VariablesCommon Dependent Variables

Arousal level (use EEG)Arousal level (use EEG)

Perceptual stuffPerceptual stuff– Flicker fusionFlicker fusion– ThresholdsThresholds– TimingTiming

Cognitive stuffCognitive stuff– MemoryMemory– vigilancevigilance

More MeasuresMore Measures

Motor tasksMotor tasks– Pursuit rotorPursuit rotor– Tapping rateTapping rate

Non humans tooNon humans too– TimingTiming– Learning and memoryLearning and memory– AvoidanceAvoidance– Paw lick testPaw lick test

ConditioningConditioning

Drug effects can be conditionedDrug effects can be conditioned

But, UR <> CR (not always anyway)But, UR <> CR (not always anyway)– If drug affects PNS, you get the opposite If drug affects PNS, you get the opposite

effect!!effect!!

Behavioural ToleranceBehavioural Tolerance– Campbell and Sieden (1973)Campbell and Sieden (1973)– Amphetamine and DRLAmphetamine and DRL