Brain Reward Pathways and Drug Dependance

Question 1

What is a drug?

Answer 1

Any substance that, when taken in to the living organism, may modify one or more of its functions/

Question 2

What is drug abuse?

Answer 2

Persistant or sporadic excessive use inconsistent with or unrelated to acceptable medical practice.

Question 3

What is drug misuse/dependence?

Answer 3

Taking of a drug which harms or threatens to harm the physical or metal health or social well being of an individual, of other individuals, or of society at large - OR which is illegal.

Question 4

What is drug dependence?

Answer 4

A state, psychic and sometimes physical, resulting from interaction between a living organism and a drug, characterised by behavioural and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience the psychic effects or avoid the discomfort of its absence. Tolerance may or may not be present. A person may be dependent of 1 or more drugs.

Question 5

What is tolerance?

Answer 5

A state of reduced responsiveness to the effects of a drug caused by its previous administration.

To maintain the same response to a drug, one must administer higher doses with repeated administrations.

Question 6

What are the 3 types of tolerance?

Answer 6

Metabolic - drug is metabolise more rapidly (up-regulation of liver enzymes)

Pharmacological - changes in receptors (down reg).

Behavioural - adapt to drug (compensate).

Question 7

What is sensitisation?

Answer 7

One gets increased responses with repeated administrations.

Question 8

Is the response to a drug dependent on anything?

Answer 8

YES! Which response you are measuring - eg if measuring effect of cocaine on mice… it would increase locomotor activity but decrease other responses.

Question 9

What is psychological dependence?

Answer 9

Overriding compulsion to take the drug despite knowing that it is harmful and regardless of consequences of the method of obtaining it.

Question 10

What is physical dependence?

Answer 10

An adaptive state manifest by intense physical disturbances when the drug is withdrawn.

Withdrawal response must be opposite effects of acute use and it treated with antagonist the response should be shorter but more intense.

Question 11

Explain the action and receptor mechanism of amphetamines.

Answer 11

Release dopamine

Gs/Gi

Question 12

Explain the action and receptor mechanism of benzodiazepines.

Answer 12

Modulator of GABAa and Glut receptors.

Ligand gated ion channels.

Question 13

Explain the action and receptor mechanism of cannabinoids

Answer 13

CB1 receptor agonist.

Gi/o

Question 14

Explain the action and receptor mechanism of Cocaine

Answer 14

Inhibit DAT

Gs/Gi

Question 15

Explain the action and receptor mechanism of ecstasy.

Answer 15

Inhibit SERT.

Gi/GO/Gq, or if 5HT3 - ligand gated ion channel.

Question 16

Explain the action and receptor mechanism of ethanol.

Answer 16

Enhance GABAa receptors.
Inhibit glutamate receptors.
LGIC.

Question 17

Explain the action and receptor mechanism of hallucinogens

Answer 17

5HT2A agonist

Gq

Question 18

Explain the action and receptor mechanism of nicotine

Answer 18

Nicotinic agonist

LGIC.

Question 19

Explain the action and receptor mechanism of opiods

Answer 19

meu-opiod agonist

Gi/o

Question 20

Nigrostriatal pathway - where does it start and end?

Answer 20

Substantia nigra - caudate nuclus

Question 21

Mesolimbic pathway - where does it start and end?

Answer 21

VTA - nucleus accumbens.

Question 22

Mesocortical pathway - where does it start and end?

Answer 22

VTA - cortex and hippocampus.

Question 23

Tubero-infundibular pathway - where does it start and end?

Answer 23

Median eminence - AP

Question 24

Explain the D1 receptor family.

Answer 24

D1 and D5.
Post synaptic.
Gs = increase cAMP = excitatory

Question 25

Explain the D2 receptor family.

Answer 25

D2,3,4.
Pre and post synaptic.
Gi/Go = decrease cAMP (alpha), increase K+ conductance (BY)…INHIBITORY.

Question 26

If you inhibit GABA what happens to the reward pathway?

Answer 26

Inhibiing GABA = increasing dopamine and reward. = Disinhibition.

Question 27

name 6 classes of drugs that increase dopamine release.

Answer 27

Amphetamines, cocaine, cannabis, ethanol, nicotine, opioids.

Question 28

Explain the action of morphine and tolerance…

Answer 28

Initally morphine downregulates ADC. After continued exposure it affects gene regulation and increases ADC.
cAMP formation initally decreases…increases to normal with tolerance but then when morphine in withdrawn there is a massive overshoot of cAMP formation.

Question 29

What are the consequences of addiction?

Answer 29

Individuals: acute overdose, poverty, AIDs/HIV, hepatitis, spticaemia, cirrhosis, bronchitis/cancer, death.
Society: crime, lost productivity, increased costs (medical and social)

Question 30

What drugs are available to treat alcohol abuse?

Answer 30

Acamprosate.
Disulfiram (Aldehyde dehydrogenase inhibitor)
naltrexone (meu antag).

Question 31

What drugs are available to treat tabacco abuse?

Answer 31

Nictoine replacement therapy.
Buproprion (antidepressant)
Varenacline (alpha4beta2 partial agonist)

Question 32

What drugs are available to treat opioid abuse?

Answer 32

methadone (meu agonist)
buprenorphine (meu partial agonist)
naltrexone (meu antag)
lofexidine (alpha 2 agonist).