Genetics; Routes of Administration

Question 1

twin studies

Answer 1

monozygotic twins have more similar rates of addiction than heterozygotic twins

Question 2

adoption studies

Answer 2

more likely to display birth family than adopted family habits
genetic predispositions

Question 3

randomized control trial

Answer 3

double-blind, randomized, and controlled clinical studies
more informed

Question 4

reward deficiency hypothesis

Answer 4

nature then nurtured
self-medicating a chronic deficiency in subjective hedonic tone that is genetic by using additive drugs

Question 5

neurobiological causes of reward deficiency hypothesis

Answer 5

1. deficiency of D2 receptors in the reward circuit = less effective signaling
2. an aberration (impaired functioning) in D3 receptors in the reward circuit
3. deficiency in presynaptic dopamine levels in the nucleus accumbens = terminals don’t release enough; affect pathway

Question 6

mice preferences for addictive drugs

Answer 6

bred mice sort themselves into high or low seeking behavioural categories by repeated exposure to addictive drugs - Lewis vs Fischer rats

Question 7

addictable mice

Answer 7

display a pathological atrophy of the neurofillamentary transport system for the dopamine synthesizing enzyme tyrosine hydroxylase in dopaminergic VTA neurons
= deficiency in dopamine synthesis

Question 8

deficiency in dopamine synthesis in addictable mice

Answer 8

concomitant aberrations in post-receptor signal transduction mechanisms compared to drug-avoidant animals
molecular event contributes to psychological effect

Question 9

striatal dopamine D2 receptor expression level - Ritalin

Answer 9

predicts subjective experience with methylphenidate
healthy male subjects with naturally high dopamine synthesis report dipleasurable experience with Ritalin
subjects with deficits in striatal D2 levels report a pleasurable experience
PET scan

Question 10

PET scan

Answer 10

measuring radioactivity - measure activity in the brain
label D2 receptors - show striatal D2 receptor level expression

Question 11

animal attributes predict vulnerability to addiction

Answer 11

high:
reactivity to stress
novelty induced locomotor activity
novelty-seeking
trait impulsivity

Question 12

epigenetics

Answer 12

chemical modifications that determine gene transcription are inherited

Question 13

human attributes predict vulnerability to addiction

Answer 13

sensation- and novelty-seeking
trait impulsivity
anti-social conduct disorder

past traumatic experiences or mood-related conditions

Question 14

Striatal D2 levels in monkeys

Answer 14

high levels in socially dominant monkeys
low levels in submissive monkeys
differences amplified in socially-housed monkeys

submissive - lower D2 receptor levels and higher vulnerability to cocaine self-administration

Question 15

impulsivity and dopamine biology pre-dispose self-administration in rats

Answer 15

reduced D2/D3 receptor expression in NAc of drug-naive high-impulsive rats
high impulsive rats display greater cocaine self-administration

Question 16

reactivity and impulsivity predict a shift to compulsive drug-taking

Answer 16

high reactivity to novelty predicts a tendency to self-administer addictive drugs
high impulsivity rats display higher compulsive cocaine self-administration

Question 17

biopsychosocial model of addiction

Answer 17

nature sets a dopamine level that is nurtured by social interactions
- drug exposure
- dopamine (and D2 receptor) functionality
- behavioural traits
- social factors (dominance)
all contribute to model of addiction

Question 18

polygenecity

Answer 18

multiple genes are involved in addiction

Question 19

predispositions

Answer 19

tendency/vulnerability to suffer from a particular condition

Question 20

link between a gene and addiction

Answer 20

genes + proteins → pharmacodynamics → physiology → behaviours

Question 21

SNPs

Answer 21

single nucleotide polymorphisms
base pair differences within coding and non-coding regions between alleles of genes in the population

Question 22

transgenerational epigenetic effect

Answer 22

methylation affects rate of transcription and gene expression → traits passed on to offspring

Question 23

studying genes

Answer 23

genome-wide association studies

dopamine networks → dopamine transporters, receptors in VTA + NAc

neuronal adhesion - important for plasticity
DNA/RNA processing
transcriptional regulation
cell structure

Question 24

addiction is viewed as a learning disease

Answer 24

addictive drugs hijack the learning/reward circuit

association between dopamine + reward → learning

Question 25

genetics x environment

Answer 25

play a 50-50 role to produce behavioural phenotypes of addiction

Question 26

routes of administration

Answer 26

inhalation (smoking) injection (IV, IM) insufflation (snorting) oral (chewing tobacco, sublingual - not swallowing) transdermal patch ingestion

Question 27

Faster absorption routes

Answer 27

faster delivery to the brain → higher peak - more dopamine; correlated with stronger high; drug does not remain in the brain for very long

Question 28

slower absorption routes

Answer 28

peak not as high, less intense high, prolonged duration in the brain - sustained release

Question 29

bioavailability

Answer 29

amount of administered drug reaching systemic circulation

Question 30

inhalation

Answer 30

drugs cross into blood by diffusion = smaller hydrophobic drugs are absorbed the fastest 7-10 second onset 2-4 hour duration 5-99% bioavailability shortest circulatory path to brain huge surface area for absorption risks: emphysema, COPD

Question 31

injection

Answer 31

10-20 second onset 2-4hr duration i.v. = 100% bioavailability 2nd shortest circulatory path subcutaneous and I.M absorption depends on diffusion into tissue and blood flow risks: necrosis, track marks, infection

Question 32

insufflation

Answer 32

10-45 min onset 5-8 hr duration - extended release up to 80% bioavailability longer pathway to the BBB risks (snorting cocaine): erosion of upper palate

Question 33

ingestion

Answer 33

20-45 min onset 6+ hour duration 5-99% bioavailability first pass metabolism; stomach pH can alter chemistry, degrade risks: irritation, emesis

Question 34

drugs must...

Answer 34

reach brain to bind receptors → effects route affects bioavailability

Question 35

abuse potential

Answer 35

quicker onset triggers greater euphoria very high: heroin IV, crack very low: hallucinogens, ingested drugs

Question 36

dose response curve

Answer 36

describe relationship between drug concentration and effects

Question 37

efficacy

Answer 37

maximal response to drug Emax

Question 38

potency

Answer 38

highest effect at lowest dose (concentration dependence) lower ED50 = more potent

Question 39

therapeutic index

Answer 39

difference in quantitative response - beneficial vs toxic response LD50/ED50 changes in the presence of other drugs

Question 40

synergism

Answer 40

additive effects - effect of multiple drugs is greater than individual effects

Question 41

antagonism

Answer 41

decreased overall response compete for binding with agonist

Question 42

drug half-life

Answer 42

time to remove 50% of [drug] from circulation

Question 43

kinetics

Answer 43

describe elimination - zero order, first order change with repeated use → tolerance

Question 44

zero order

Answer 44

linear curve of elimination

Question 45

first order

Answer 45

exponential curve of elimination