Behavioral Pharmacology

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Behavioral Pharmacology

• Studying drug effects on behavior
• Objectively defined behavior
• Objective measurement system
• Dose range
• Control conditions (placebo)
• Each subject gets all doses
• Visual inspection of data

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Behavioral Pharmacology
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Behavioral Pharmacology
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Chronic Effects of Drug on Aggression
Drug
Drug
Placebo
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Acute Effects of Thorazine on responding under FR
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NOTE Single sessions at each dose in BBCD
sequence.
BBC 10mg BBC 40mg BBC 20 mg BBC 40 mg BBC 10 mg
BBC 20 mg
BBC 10mg BBC 20mg BBC 40 mg BBC 40 mg BBC 20 mg
BBC 10 mg
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Assays DMTS
Choice stimuli
Sample stimulus
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DMTS Start
FR 5
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Delay with no stimuli Delay 0, 4, or 8
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Repeat trial
Snack
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DMTS as a Function of Drug and Delay
NOTE BBCD
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Exercises

• In DMTS, what is presented first?

• Then...

• Then...

• Then...

• DMTS is a study of .

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Repeated Acquisition
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Repeated Acquisition Measures

• Rate of response
• correct
• trials to mastery
• minutes to mastery

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Repeated Acquisition Data
NOTE BBCD with 2 determinations at each dose
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Exercises

• Giving drugs during repeated acquisition is an
  assay of drug effects on _______

• Participants learn to _________

• One dependent variable in repeated acquisition is
  ___________

• BBCD stands for _________

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Drug Discrimination

• Initial Training
• Train S to press right button if experiencing
  d-amphetamine
• Train S to press left button if experiencing
  placebo

FR 20 if drug day
FR 20 if placebo day
Choice
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Drug Discrimination

• Testing
• Give test drugs at various doses to test for
  similar stimulus properties
• If FR 20 (right button) is pressed, then the drug
  feels similar

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Drug Discrimination

• Testing
• Give test drug
• See what key is pressed

Feels Like training drug
Does not Feel like training drug
Choice
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Exercises

• The purpose of a drug discrimination study is to
• The SD in drug discrimination studies is
• Training Drug is d-amphetamineTesting Drug
  is cocaineIf chooses the drug button Conclusion?

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Phase Years Population Purpose Success Rate
PreClinical 3.5 Lab and animals Safety and bio activity 5000 tested
Phase 1 1 20-80 Healthy Volunteers Safety and dose 5 enter
Phase 2 2 100-300 patient volunteers Efficacy and side effects 5 enter
Phase 3 3 1000-3000 Efficacy adverse reactions to longer term use 5 enter
FDA 2.5 Review and approval 1 approved
Phase 4 Additional post marketing study required by FDA
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10 mg
15 mg
5 mg
5 mg
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Poling

• Behavior change meds mechanism not well
  understood
• We know about NT, but not link with behavior.
• 4 essential features of a drug evaluation?
• DV
• Meds given according to protocol
• Design
• Data analysis must be adequate

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Poling

• Prescribing drugs to special populations in need
  of protection should involve safeguards.
• Goals are clear with specific targets and in P
  interests
• Tx decisions made on basis of drug effects
• Flexible and integrated with beh Tx.

• 3 design factors
• Single vs repeated observations
• Between vs within
• Stats vs visual

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Poling

• 3 design factors
• Single vs repeated observations
• Pre-post testing vs daily recording
• Between subject vs within subject
• Between either Tx or P
• Within each subject gets all conditions
• Stats vs visual
• T tests, F tests vs visual inspection

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Poling

• Fig 9-3.
• Use of anti-psychotics w/MR
• Many drug studies not well done
• Measurement
• Design
• Dose range
• Data recording methods See Fig 9-5.

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Poling

• MPH study Fig 9-4
• DV
• Design concerns
• Results
• Inter-subject replication

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Poling

• Clozaril study Fig 9-6
• Random assignment to 1 or 2 groups Clozaril vs
  Thorazine. Rating scales used.
• Other studies are correlational take people
  with drug and those without, and then compare
  behavior.

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Poling

• Between vs within subject designs
• Depends on the kind of question
• Predictions of affected
• Nature of effects

• Behavioral mechanisms of drugs
• All behavioral functions of other stimuli
• MO, SD, CS, US, reinforcers, punishers

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Poling
Review

• 3 design factors
• Single vs repeated observations
• Between vs within
• Stats vs visual

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Poling
Review

• Difference between typical and atypical
• Affinity for D1/D2 vs D3/D4
• Behavioral mechanisms of drugs
• MO
• SD
• Reinforcer/punisher
• CS
• US

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McKim Cannabis
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McKim Cannabis

• Source- plants
• Active ingredient - THC
• Hashish - dried resin from top
• Hash oil?
• Boil hash in alcohol, filter out residue, allow
  alcohol to evaporate (cannabinoids are soluble in
  alcohol)
• Thai sticks buds bound with string onto short
  sections of bamboo or stems
• Spread by Scythians in 200 BC
• Also known in China 6000 years ago

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McKim Cannabis
Scythians There is nothing new or strange in
what we do. We follow our mode of life in
peaceful times. We have neither towns nor
cultivated lands in these parts which might
induce us, through fear of their being ravaged,
to be in any hurry to fight you. But if you must
needs come to blows with us speedily, look about
you, and behold our fathers' tombs. Attempt to
meddle with them and you shall see whether or not
we will fight with you."
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McKim Cannabis
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McKim

• Kinetics
• Administration/Absorption
• Slow absorption orally
• Fast if inhaled
• Distribution
• Lipid soluble so goes everywhere
• Collects in liver, lungs, intestines
• Metabolism
• Liver
• Many metabolites some are active
• Excretion
• T ½ - biphasic 30 min then 20-30 hours

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McKim

• Neuropharmacology
• CB1 found in CNS
• CB2 found in spleen and immune system
• Endogenous cannibinoids THC is stronger
• Potentiate NE, DA, SE, ACH, endogenous opiates
• Effects on body
• dilation of eye vessels, hunger, dry mouth,
  increase in HR
• Medicinal uses
• decrease in intraocular pressure, anti-emetic,
  movement disorder, spasticity, analgesia

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McKim

• Other effects
• Sleep will increase, but can disrupt on high
  doses
• Perceptual effects can disrupt time
  discrimination, decrease pain
• Many things appear funny, dreamy state
• Memory problems disrupts short term memory
• Attention disrupts attention
• Driving problems with attention
• Aggression decrease
• Immune system may depress

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McKim

• Relation to Korsakoffs syndrome?
• Korsakoffs is seen in alcoholics and has memory
  problem and disorientation.
• Caused by damage to hippocampus, which has CB
  receptors
• Cannabis may block functions of hippocampus
• Tolerance
• Non-humans yes
• Humans sensitization? some tolerance
• W/D syndrome
• Increase in anxiety, restlessness, irritability
  AO for food

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McKim

• Health risks
• Will not produce psychosis. But, will increase
  intensity of schiz symp or paranoia
• Effects on brain or intellectual functioning?
• Rats yes
• Monkeys no
• Humans no. But might be problems in memory and
  attention.
• Amotivational syndrome?
• NH some evidence in PR schedules
• Humans none.

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McKim

• Gateway drug?
• No.
• Lung cancer?
• There are 50-70 more carcinogenic material.
• Decrease in testosterone
• It may potentiate cigarette smoke
• Weakens immune system

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McKim

• Study by Kelly et al. wherein participants
  smoked placebos as often as 2.3 THC.
• Single access vs choice
• What was the reason for this outcome?
• What is more sensitive procedure was for
  assessing preference

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Poling
Review

• Source of cannibis
• Marijuana plant
• Receptors
• CB1 CB2
• Effects
• Dilation of capillaries in eyes
• EO for food
• Dry mouth
• Increase HR

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McKim Hallucinagens

• LSD
• Hallucinogen class similar to serotonin
• Source synthetic drug, but similar chemicals
  exist in ergot fungus that infects grains
• SE agonist/antagonist
• Kinetics
• Oral administration absorbed in stomach
• Metabolized? Liver
• T ½ - 2 hours
• Typical dose 300 mics or less
• Effects dilation of pupils, hallucinations,
  early sweating, nausea, jaw grinding
• Not lethal

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McKim

• Psilocybin
• Hallucinogen class similar to serotonin
• Source mushrooms
• Duration of action 4-6 hours
• Dose 4-8 mg
• Mechanism SE agonist/antagonist
• Not lethal

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McKim

• Mescaline
• Hallucinogen class similar to NE
• Source cactus called peyote
• Ceremonies by Native American Church
• Usual dose 200 mg
• Effects nausea, dilation, hallucinations
• Not lethal

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McKim

• MDMA/MDA (ecstasy)
• Hallucinogen class similar to NE
• Usual dose 100 mg
• Effects euphoria, state of well being,
  talkative, EO for everything
• High dose may deplete serotonin
• Sleep problems, anxiety, hostility,
  impulsiveness, selective impairment of
  memory/attention, depression, heat regulation
• Typical use rave drug
• Mechanism causes release and blocks re-uptake
  of SE, NE, DA
• heart, liver damage, hyponatremia (low blood NA
  from drinking excessive water)

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McKim

• Atropine Similar to ACH
• Anticholinergic
• Dilates pupils
• Used pre-surgically to reduce drooling/secretions
• Increase HR for bradychardia

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McKim

• PCP
• Source synthesized angel dust
• Use originally an anesthetic and analgesic
• Effects -trancelike state, disorientation,
  fear/anxiety, some psychosis
• Blocks NMDA receptor, which is excitatory resp
  for reinforcing effects
• PCP has its own receptor on the NMDA receptor
• When PCP occupies, it blocks the ion channel NE,
  DA, ACH, SE
• Lethality problem TI of 10
• Long term psychosis

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Poling
Review

• 3 classes of hallucinogens
• SE LSD/psilocybin
• NE Mescaline/Ecstasy
• ACH - atropine
• Effects of LSD
• Hallucinations
• Pupil dilation
• Sources
• LSD synthetic
• Mescaline peyote
• Psilocybin - mushroom

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Poling
Review

• Health risks
• Ecstasy
• Serotonin depletion
• Dehydration
• Heart trouble
• PCP
• Psychosis
• Lethal

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Standard Chart
10 behaviors in 10 minutes
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Standard Chart
100 behaviors in 50 minutes
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Standard Chart
5/minute and observed for 1 minute
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Therapeutic and Toxic Effects
Therapeutic
Toxic
Responding
ED99
TD50
TD1
ED50
Dose
Indices
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Lidocaine Quantal Dose-Effect
Achieving Complete Analgesia
Total Lidocaine Dose (mg)
Ferrante et al. Anesth Analg 8291-7, 1996
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SIB Naltrexone effects
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SIB Naltrexone effects
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SIB Naltrexone effects
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SIB Naltrexone review

• Criteria for inclusion
• Primary focus was the effect of naltrexone
• Ss were diagnosed with ID
• SIB was measured
• Peer refereed English language journal
• Results were in a quantitative format
• Short-term or acute trials

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SIB Naltrexone effects
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SIB Naltrexone effects
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D-Amphetamine as SD/SDP
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Risperdal Effects on matching
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MPH FA Results
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Neurogenesis Factors