Addiction

Question 1

What are the common pathways activated by all drugs with addictive potential?

Answer 1

The pathway consists of a dopamine cell in the VTA (in the midbrain) synapse at the NAc (forebrain) release DA.

Question 2

True or False: In order to understand a problem we must define it

Answer 2

True

Question 3

True or False

The definition of a problem influences its treatment.

Answer 3

True

Question 4

Compare addiction to another epidemic

In class we compare addiction to ___________.

How is it defined in traditional healthcare circles?

Answer 4

Diabetes (type II)

Definition: Diabetes is a chronic progressive disease involving poor of blood sugar (too much sugar in the blood)

Question 5

How has the standard definition of T2DM lead to treatment?

Hint: What is the model that was created from the traditional definition of Diabetes?

Answer 5

Model:

Increase Blood Glucose is toxic to our tissues and this problem is due to Insulin Resistance. The cells do not take accept insulin which is needed to shuttle glucose into cells.

Treatment

Basically, for every health care problem, we give one pill or one procdure.

The treatment consists of Oral Agents and Injectetables

Metformin –> Decrease Glucose from liver

Sulfonylureas –> stimulate B cells in Pancreas –> Increase Insulin

Insulin

If lucky, provided a diet and exercise plan

Question 6

Is the current treatment of T2DM effective?

Answer 6

Insulin Resistance is not the only reason why glucose is not going into cells.

Also, Blood glucose doesn’t rise until after the pancreas fail

Question 7

What is a better description of the problem of T2DM and how would this new understanding of the problem change the treatment?

Answer 7

In this model, we do not focus on only blood glucose but total glucose, and not insulin resistance –> Hyperinsulinemia (too much insulin)

The excess glucose is converted to fat (denovolipogenesis); primary by the liver

Treatment

The only one that works is Metformin ( decrease Glucose from the liver)

provided Sulfonylureas and Insulin are a poor solutions

Question 8

How do we define addicition?

Answer 8

A chronic progressive relapsing disease

Question 9

Are there parallels between T2DM and addiction in terms of definitions and approaches to treatments?

Answer 9

Addiction and Diabetes have high relapsing rates.

Also, eating is behavior, and taking drugs is behavior so you have the controlled to stop the continuous usage.

Question 10

What can we learn from one of these problems about the other?

Answer 10

How do we find a solution to the problem?

We figure out that in the one epidermic we can use that knowledge to trust the addiction epidemic.

Question 11

What are the common ways of describing addiction?

Answer 11

Compulsive drug use regardless of the detrimental effects of the behavior on various aspects of health and life.

Question 12

Again, words matter – why do we use the term relapse for addiction but not other common healthcare issues?

Answer 12

The struggle and try to solve the problem and return back to the usage of the drug.

Question 13

What factors influence the likelihood of developing addiction (does this differ from that of T2DM?)

Answer 13

Environment

Chaotic home and abuse

Parent’s use and attitudes

Peer influences

Community attitudes

Poor school achievement

Biology/genes

Genetics

Gender

Mental disorders

Drugs

Route of adminsitarion

Effect of the drug itself

Early use

Availability

Cost

Question 14

What are some of the neuroadaptations described consequent to repeat drug exposure?

Answer 14

Decrements in prefrontal cortical functioning

The anatomical shift in the dominant pathways of DA signaling VTA –>NAc

SN–> Straitum

Increased DA release from drug cue, increasing value

Molecular changes in extended reward circuit

Adaptations in brain stress system

Question 15

What is the Reward Pathway and how did we find it?

Answer 15

This is done in an experiment on both humans and rats

Question 16

What does dopamine release in the nucleus accumbens actually signal?

Answer 16

Dopamine is signaling motivated behavior.

Question 17

Be familiar with the various functional circuits that are relevant to the development of addiction.

Answer 17

The prefrontal cortex is the thoughtful pathways to go and stop

The striatal pathways are the goal-directed behavior

The external context contain the memory –> which weighs in on your decission

Internal context –> consit of the insula check out your internal state

Question 18

What are the Blunted response displayed by most long term users ?

Answer 18

Midbrain to Forebrain DA signals shift in favor of more rigid habitual responses

Question 19

How does the prefrontal circuit and LTP play into the valuation of drug rewards compared to another reward?

Answer 19

Dopamine performs the cellular modification, The D1R, and GLUN1-NMDAR will be release by dimerized. NMDA receptor moves toward the spine and set at the glutamate synapse and drive LTP

Question 20

How does dopamine release in PFC drive craving?

Answer 20

In the PFC (sub-regions for drive/motivation) with excess DA release associated with chronic drug use, Ca2+ activated K channels become disabled leading to increase excitability which causes the craving.

Question 21

Where do choice and decision-making fit into addiction? Which part of the brain influences these functions?

Answer 21

Happens in the Pre Frontal Cortex and things to consider which making decision is the

value of the reward

relative value compared to other rewards

timing of available rewards

probability of actually getting available rewards

the effort required for possible rewards

Risk of behavior necessary

Question 22

How does the consistent finding of a drug-induced decrease in expression of dopamine receptors relate to the concept of hypofrontality ion addiction?

Answer 22

Question 23

How do progressive changes in the function of relevant neural circuits with addiction relate to our understanding of the behaviors commonly associated with someone suffering a substance use disorder?

Answer 23