Lecture 20

Question 1

What is the name of the brains reward centre

Answer 1

The nucleus accumbens

Question 2

What is the effect of the release of dopamine into the nucleus accumbens

Answer 2

A sense/feeling of euphoria

Question 3

Define a stimulant

Answer 3

Drugs that increase locomotion, wakefulness and cognition by increasing release of dopamine

Question 4

What are the 2 strongest types of stimulant

Answer 4

Dopamine releasing agents followed by NDRI’s

Question 5

What are the causes of tolerance

Answer 5

Change in receptor function/desensitization eg. NAChR

internalisation of receptors(most common cause)- causes fewer dopamine receptors to be expressed in the nucleus accumbens

internalisation of transporters

exhaustion of mediators eg. running out of cAMP (RARE)

increased drug metabolism eg. for alcohol (RARE)

Question 6

What can cause internalisation of receptors

Answer 6

consistent overstimulation can cause the receptors to become triggered to internalise

Question 7

How does the receptor downregulation impact neurotransmission

Answer 7

Having fewer receptors on the post syn causes the NT release to activate lower numbers of receptors which results in lower response in intracellular signalling

E.g. fewer D1 GPCR available means less cAMP will be produced causing an overall lower response to a stimuli

Question 8

What are the main receptors involved in drug abuse

Answer 8

Dopamine,

Alpha(Noradrenaline),

Serotonin,

NMDA(glutamate),

Opioid,

GABA,

Cannabinoid,

Nicotinic(acetylcholine)

Question 9

Describe the dopamine release pathway in the brain

Answer 9

The Ventral Tegmental area (VTA) releases dopamine where it will either go to the nucleus accumbens which contains receptors and cause a euphoric feeling or go to the prefrontal cortex and enhance cognition

Question 10

Describe the impact of surprise on the VTA

Answer 10

Having a positive surprise will result in the VTA releasing a large spike of dopamine creating strong response in the nucleus accumbens allowing lots of euphoria

Question 11

Describe the relationship between assumed rewards and VTA

Answer 11

If something assumes to be receiving a reward and then there isnt one, VTA activity actually plumments creating an aversion

Question 12

Whats the difference between tonic and phasic dopamine receptor firing when it comes to drug dependence

Answer 12

tonic is a baseline level of dopamine firing meaning its much less likely to cause a dependence

Phasic also known burst is a large increase in a short moment causing it to be much more likely to cause a drug dependency

Question 13

Do all dependence drugs need to increase dopamine

Answer 13

NO, most but not all require the increase in dopamine

Question 14

What types of drugs are NDRA’s and how do they increase dopamine

Answer 14

amphetamine and methamphetamine are NDRA’s. They function by entering vesicles and pushing dopamine and noradrenaline into the synapse.

These high numbers in the synapse cause more activation of receptors

Question 15

Why is the NDRA Methamphetamine more of a dependency risk than Amphetamine

Answer 15

Methamphetamine enters the brain more rapidly as its more lipophilic, this allows it to push the NT out faster than amphetamine would

Question 16

Why are SRA’s less likely to cause a drug dependency than NDRA’s

Answer 16

SRA’s such as MDMA function in the exact same way as NDRA’s however they push serotonin into the synapse rather than dopamine

Question 17

What type of drug is cocaine and how does it work

Answer 17

Cocaine is an NDRI along with ADHD medication, they work by stopping the transporters that reuptake the dopamine and noradrenaline from the synapse. Therefore keeping it binding to receptors for longer

Question 18

Whats the relationship between speed of drug delivery and addiction (for NDRI and NDRA)

Answer 18

The faster the speed of of drug delivery the more addictive, the higher the self dosage, higher chance of loss of control and overdosing

speed of delivery has also been found to alter some gene expression pathways in neurons

Question 19

Which dopamine receptor is in charge of the high and how does it work and differ to the other

Answer 19

D1 are in charge of the high and are the second to activate in the presence of dopamine. It’s lower affinity means that the numbers of dopamine need to be enough to occupy all the D2 and then be able to activate D1 to get the high. This only happens with phasic release

D2 is high affinity and does not contribute to a high

Question 20

Can different consumption methods of NDRI’s and other drugs have different effects

Answer 20

Yes, IV and oral consumption of methylphenidate (an NDRI) was compared and found to activate different regions of the brain while also having a different “high” rating

Question 21

Whats the percentage of genetic component that contribute to stimulant dependence

Answer 21

dependence to stimulants is a 50% genetic predisposition

Question 22

What percentage of first time users go on to form a dependence

Answer 22

10-15%

Question 23

Physical dependence causing withdrawal that can result in death for what drugs

Answer 23

alcohol and benzodiazepines. This happens because these drugs increase GABA activity so when you withdraw your receptors are desensitized to a normal level of GABA which can result in seizures

Question 24

What type of opioid is used to help opioid addicts overcome addiction

Answer 24

The partial agonist buprenorphine