Reward and the brain

Question 1

What is the background of reward and how it shapes behavior?

Answer 1

• the pursuit of rewarding experiences drives behavior
• early in life, behavior is driven by immediate reward: food
• as we mature, more value is placed on long-term rewards: grades
• reward-seeking is beneficial and helps to focus our attention and behavior
• it can be maladaptive and lead to risky/poor decision making: excessive gambling, drinking, drug-taking

Question 2

What is the brain reward pathway?

Answer 2

Mesolimbic dopaminergic pathway
Enters the Ventral tegmental area (VTA), and dopamine then goes into the amygdala and nucleus accumbens

Question 3

What are endogenous ligands?

Answer 3

Neurotransmitters or hormones inside the body that bind to receptors (dopamine, acetylcholine, estrogen, cortisol)

Question 4

What are exogenous ligands?

Answer 4

Drugs or toxins from outside of the body that bind to receptors (heroin, nicotine, THC)

Question 5

How do drugs of abuse work?

Answer 5

Drugs have their effects by “tapping into” the brain’s naturally-existing reward circuitry
- increase neurotransmitter release
- block neurotransmitter reuptake
- alter neurotransmitter packaging in vesicles
- activate receptors

Question 6

What did the Nuggets video show us about addiction?

Answer 6

• it is usually seen as a choice, but it actually becomes a reliance
• effects get smaller and smaller
• usually seen as bad people but usually they are good people
• bad effects increase and may not be noticed at first isolation

Question 7

What is addiction?

Answer 7

A chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful or adverse consequences
- it is considered a disease because drugs change the brain structure and function
- the effects can be long lasting, if not permanent

Question 8

Why do people take drugs?

Answer 8

environment (“norm”)
ease of access
social settings
genetics
- to feel good
- to feel better
- to do better
- prior medicinal use
- curiosity, and “because others are doing it”

Question 9

What issues arise from drug use?

Answer 9

• Drug use can quickly take over a person’s life
• they require more and more drug to feel “normal”
• formerly pleasurable activities become less pleasurable
• they continue to seek out and take drugs, even with severe consequences

Question 10

How does Dopamine change reward circuitry in the brain?

Answer 10

The brain adjusts to the overwhelming surges in DA by producing less and less of it, or reducing the number of receptors (downregulation)
- this alters the reward circuitry and the ability to experience pleasure is reduced
- this is also why the user is unable to enjoy things that previously brought them pleasure and feels lifeless and depressed
- Addicts need to take drug just to be able to elevate their DA levels back to normal levels

Question 11

How are dendritic spines changed through drug use?

Answer 11

• long-lasting changes
• changes in spine density and branching in NAc
• alterations in neurotransmitter release
• altered receptor numbers and functioning

Question 12

Who becomes addicted?

Answer 12

• No single factor determines who will become addicted
• environmental factors: home and family, peers and school, age at first use
• certain characteristics or phenotypes can contribute to increased drug abuse vulnerability
• Biological factors: prior stress history, character traits, sex, hormone state

Question 13

What are some sex differences in drug taking?

Answer 13

• 9 million women have used illegal drugs in the past year in the USA (40% of drug addicts are now women)
• 3.7 million women in the USA have taken prescription drugs non-medically during the past year
• among cocaine users 12-17 years old 51.5% are women, in the 18-25 age group 42% are women, for cocaine users 26 and older 38.8% are women

Question 14

Is use a good indicator of addiction? (sex differences)

Answer 14

• Time from first exposure to drug to chronic drug use is shorter for women
• Females present for treatment sooner are consuming more cocaine than men
• reasons for initiation of drug use are different for women vs. men:
  
  • women: self-medication for depression, stress, anxiety
  • men: risk-taking, in-group behavior

Question 15

Why are there sex differences in addiction?

Answer 15

Influence of culture and society
influence of hormones
influence of developmental differences
combined influence of multiple factors

Question 16

How do hormones affect sex differences in addiction?

Answer 16

• Gonadal hormones act during early life and puberty to “organize” the brain
• During adulthood hormones act on sexually differentiated brain structures to activate specific behaviors

Question 17

How do sex differences in addiction happen?

Answer 17

• Males and females may exhibit sex differences in behavior because they secrete different hormones
• Males and females may exhibit sex differences in behavior because males and females have different brains due to developmental influences
• Males and females may exhibit sex differences in behavior because they secrete different hormones and because males and females have different brains due to developmental influences

Question 18

What has been found from using animal models to study addiction?

Answer 18

• using operant response to look at drug taking behavior
• female rats acquire drug taking faster than male rats
• estradiol enhances cocaine intake in females but not males
• estradiol enhances motivation for cocaine
• estrogen enhances the behavioral response to cocaine in females
• More females than males develop a preference for cocaine over food
• Gonadectomy reduces the dopaminergic response to cocaine in females but not males
• Estradiol acts directly in the stratum to rapidly enhance DA release in females but not males

Question 19

How does estrogen enhance the behavioral response to cocaine in females?

Answer 19

• repeated administration of cocaine results in a progressive enhancement of the behavioral response associated with addictive behaviors and/or craving
• females sensitize more and at a faster rate
• estrogen enhances sensitization

Question 20

How does estradiol enhance striatal dopamine release?

Answer 20

• Classical receptors take hours/days to have physiological effect
• must be a different type of receptor that is responsive to estradiol in the striatum
  (the membrane-bound receptor seems to enhance DA downstream–> E binds to MB receptor)
• estradiol inhibits GABA neurons
• This leads to disinhibition of dopamine neurons and enhanced dopamine release

Question 21

What are some sex differences in reactions to drug taking?q

Answer 21

• males show greater physical and motivational signs of withdrawal from alcohol than do females (ethanol withdrawal increases CORT release in males but not females)
• Women show greater propensity to relapse for most drugs of abuse, with shorter periods of abstinence
  
  • They exhibit increase reactivity to internal (emotional) and external (drug-associated) cues
• Some pharmacotherapies aimed to reduce the subsequent drug-taking work in men but not women