HSW296: Neuropsychology of Addiction

Chapter 1: Some Basic Pharmacology

DRUG TERMS
Definition of a drug
Names for drugs
Chemical name
Generic name
Trade/Brand name
Street name

DOSAGES
Dose-response curve = “DRC”
What is it
How do you read it?
Threshold
ED50
LD50
Therapeutic Index (Know how to define it, calculate it and interpret it)

IMPORTANT DISTINCTIONS
Difference between effectiveness of a drug and the potency of a drug?
Difference between primary effect of a drug and the side effect of a drug?
Difference between pharmacokinetics and pharmacodynamics?
Difference between three types of drug-drug interactions:?
Antagonism
Additive
Super-additive or potentiation

“ADME” (Absorption, Distribution, Metabolism Elimination (or Excretion)

ROUTES OF ADMINISTRATION
Parenteral
Vocabulary
Vehicle
Absorption
Physiological saline
Bolus
Vein, artery, capillary
Depot injection
Types of Parenteral Routes
Subcutaneous (s.c.)
Intramuscular (i.m.
Intraperitoneal (i.p.)
Intravenous (i.v.) (mainlining)
 Inhalation
Gases
Principle of diffusion
Smokes and solids
Intranasal administration or “insufflation” or “snorting”
(This pathway to absorption is unclear: mucous membranes, lungs, and stomach)
Oral (p. o.)
Swallowing
Buccal membranes or mucous membranes (does not go through digestive system)
Transdermal
Epidermis
Patches (nicotine and others)
LIPID SOLUBILITY (Several characteristics influence a molecule’s “lipid solubility”; one is whether
the molecules are charged or not)
Olive oil partition coefficient
pKa

DISTRIBUTION OF DRUGS
Lipid solubility
Blood-brain barrier
Non-lipid-soluble substances and “transport mechanism”
Passive Transport
Channel that allows non-lipid soluble molecules to pass through in response to
diffusion
Carrier protein
Active transport—expenditure of energy
Protein binding
Placental barrier

ELIMINATION (Metabolism and excretion)

Dynamic duo
Metabolic enzymes
Metabolic process = detoxification
(e.g., Alcohol-alcohol dehydrogenase-acetaldehyde; Acetaldehyde-aldehyde dehydrogenase-
acetic acid

First-pass metabolism
Rate of elimination
Half-life (first order kinetics)
(vs zero-order kinetics)

FACTORS THAT ALTER DRUG METABOLISM

Enzyme induction
Depression of enzyme systems
Age
Gender
Species
Time course
Therapeutic window
Chapter 2: Behavioral Analysis of Drug Effects
HISTORY OF BEHAVIORAL PHARMACOLOGY

Criticism of the verbal description of subjective experiences

Psychologists who developed techniques to measure behavior: Pavlov, Thorndike, and Skinner

Behavioral pharmacology (combination of the work of pharmacologists and behavioral

psychologists; Peter Dews and Joseph V. Brady

Psychoterapeutic revolution (class of drugs known as phenothiazines with Chlorpromazine

(Thorazine) as the main drug ; advanced due to behavioral experiments such as the one by Macht
with the “escape-avoidance” task as the outcome variable of interest.

Dews further applied operant conditioning techniques to study the effects of sedatives

RESEARCH DESIGN

Experimental versus non-experimental research? Defining feature?

Experimental research
Independent variable
Dependent variable
Control condition
Placebo control condition
Placebo effect
Standard three-group design—comparisons of interest?
Experimental bias—double blind-
Non-experimental research
Limitation?
Necessary?

MEASURING UNCONDITIONED BEHAVIOR OF NONHUMANS

Spontaneous motor activity (SMA) in an open field

Stereotyped behavior
Inclined plane test to measure muscle tone
Elevated plus maze to measure anxiety
Paw lick latency test to measure analgesia

MEASURING CONDITIONED BEHAVIOR OF NONHUMANS

Classical conditioning: UCS UCR CS CR (Pavlov)
Operant conditioning—Skinner
principle of reinforcement (positive and negative) to increase behavior
principle of punishment (positive and negative) to decrease behavior
Continuous vs intermittent (partial) reinforcement
Schedules of reinforcement
Ratio versus interval
Fixed versus variable
Avoidance-escape task as measured by a shuttle box with an electrified grid floor or the pole-
climbing task
STIMULUS PROPERTIES OF DRUGS—Non-humans
Dissociation or state-dependent learning
(e.g., In T-maze experiment, rat that could avoid shock when on same drug as during training, could
NOT avoid shock if not in drug state)
Discrimination possible between classes od drugs
Discrimination possible between drugs within a class?
Discrimination possible between doses of same drug?
Stimulus discrimination versus stimulus generalization

REINFORCING PROPERTIES OF DRUGS—ABUSE LIABILITY—Non-Humans

Rate of responding
Progressive ratio schedule of reinforcement
Choice
Conditioned place preference

MEASURING BEHAVIOR EXPERIENCES OF HUMANS

Subjective effects
Rating scales (Visual Analogue scale, or normal rating scale)
Drug State Discriminaton (Remember = humans)
Perception (absolute threshold, difference threshold, critical frequency at fusion)
Motor Performance (simple reaction time, complex reaction time, pursuit rotor, finger
tapping rate
Attention and Vigilance (Mackworth clock test)
Memory (short term memory, working memory, long-term memory)
Tests of response inhibition
Driving
DEVELOPMENT AND TESTING OF PSCHOTHERAPEUTIC DRUGS

Food and Drug Administration (FDA) approval of drugs

Lab tests
Screened with animals = pre-clinical (establish ED50 and LD50 for therapeutic index, etc.)
Clinical testing
Phase 1 health humans for toxicity and side effects
Phase 2 patients but no control group
Phase 3 “controlled clinical trials”; now drug can be licensed and marketed
Phae 4 after sales evaluation
Off Label Use
Chapter 3: How We Adapt to Drugs—Tolerance, Sensitization, and Expectation

TOLERANCE
Mithridatism

We do not develop tolerance to all of the effects of a drug at the same rate.

Acute tolerance

Cross tolerance

MECHANISM OF TOLERANCE
Pharmacokinetic tolerance

Pharmacodynamic tolerance

Functional disturbances--tolerance will develop more easily in a circumstance where a drug

places a demand on an organism’s homeostatic mechanism

Behavioral Tolerance—discussed later in chapter

WITHDRAWAL
Different drugs produce different withdrawal symptoms—typically they are the opposite of
the effects of the drug.

Withdrawal symptoms are stopped by taking the drug or a drug from the same class =
“cross dependence”

“Dependence” originally = (1) discontinuation of a drug = withdrawal symptoms or (b) a

state in which one compulsively takes a drug

But now known that people can take drug compulsively even with no withdrawal
symptoms and people can experience withdrawal symptoms and yet not take drug
compulsively. So now only definition for “dependence” to be used correctly is the presence
of withdrawal symptoms: so the following three terms are to be seen as synonymous:
Physical dependence, physiological dependence, or just dependence.

Opponent process theory

Compensatory effects

CONDITIONING OF DRUG EFFECTS

Classical conditioning
Drug effects and stimuli

Compensatory responses

Drug tolerance
Withdrawal
 Operant conditioning

Operant conditioning of drug tolerance

SENSITIZATION
Stereotyped behaviors

Cross- sensitization

Mesolimbic dopamine system

EXPECTANCY AND CONTEXT

Placebo effect

Expectation mechanism (top-down pain0relieving pathway

Factors modifying the placebo effect

Strength of their belief
Desire for the outcome

Nocebo effect (generation of side effects)

Self-administration = stronger effect of drug than administration by others

Novel enironments