Lecture 1: Neurobiology

Question 1

Nucleus Accumbens

Answer 1

• Plays significant role in the cognitive processing of motivation, aversion, reinforcement learning, ande reward (incentive salience, pleasure, and positive reinforcement).
• Plays a significant role in addiction.

Question 2

Ventral Tegmental Area

Answer 2

• Part of Midbrain (transverse at level of superior colliculi).
• The origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways
• Widely implicated in the drug and natural reward circuitry of the brain. Plays important role in cognition, motivation, orgasm, love, as well as several psychiatric disorders.
• Its neurons project to numerous areas of the brain, prefrontal cortex, caudal brainstem and several other regions.

Question 3

Neural/Neurobiological Substrate

Answer 3

Term used in neuroscience to indicate the part of the central nervous system (brain and spinal cord) that underlies a specific behavior, cognitive process, or psychological state.

ex: “The _______ ________ responsible for tolerance and withdrawal overlap, since withdrawal only occurs in patients who have developed tolorance”.

Question 4

Tolerance

Answer 4

The need to take increasingly large doses of drug to achieve the same result.

Question 5

Withdrawal

Answer 5

A (group of) negative responses/symptoms that occur upon the abrupt discontinuation or decrease in intake of medications or recreational drugs.

Question 6

Exogenous

Answer 6

From the outside

Question 7

Epidemiology

Answer 7

the branch of medicine which deals with the incidence, distribution, and possible control of diseases and other factors relating to health.

Question 8

Orbital Frontal Cortex | Amygdala | Anterior Cingulate Cortex

Answer 8

Part of brain linked to drug and cue inducing craving states, along with ________ and ________ ______ ______

Question 9

Changed Set Point Model

Answer 9

Drug use alters a biological or physiological baseline or set point.

1. Mesolimbic reward paths reset so that DA reduced for normal pleasurable activities. A similar reset occurs in the LC but in opposite direction, so that NE release increased during withdrawal.
2. With repeated use the response to augmented DA is more numerous, strengthened inhibitory auto-receptor control which leads to decreased basal DA. DA deficiency produces dysphoria.
3. Drug induced sensitization to drug-associated cues that leads to “wanting”.

Question 10

Cognitive Deficits Model

Answer 10

• Those who develop SUDs have abnormalities in prefrontal cortex which compromise signaling to mesolimbic rewards system.
• PFC; regulation of judgement, planning; impulse control
• PFC sends inhibitory signals to mesolimbic system
• Repeated drug use causes further damage.

Question 11

quicker / more addictive

Answer 11

The ______ neurochemical reaction (efftct) occurs in the brain, the ______ _____ a substance tends to be.

Question 12

Cravings

Answer 12

Predict relapse; often observable on scans as prefrontal cortex activation.

Question 13

Prefrontal cortex

Answer 13

Generally shows activation deficits and structural abnormalities in cases of drug addiction. Often other things become less pleasurable.

Question 14

Schizophrenia and/ Bipolar Disorder

Answer 14

Individuals with ______ and _____ disorder tend to have more severe symptoms when using when using illicit drugs

Question 15

Variant 1: Norepinephrine

Answer 15

• Our system is naturally set to give a healthy amount of pleasure
• With addiction, the system down-regulates its own pleasure-maintenance work as it learns to “expect” the high external pleasure source(s):
• No longer sends info to prefrontal, amygdala
• General dopamine response gets reduced • Locus coeruleussends withdrawal signals

Question 16

Variant 2: Dopamine

Answer 16

With addiction, increase in tonic dopamine reduces phasic dopamine release from VTA (it doesn’t think it needs to).

• TD hits side of neuron which does not fire but it thinks it has; now neurons think they’re responding to dopamine but are not.
• General dopamine response gets reduced
• Low dopamine leads to dysphoria, withdrawal

Tonic = spilt from neighbouring cells which makes the cell THINK it has had a pleasure spike already
Phasic = activation cells cause pleasure spike

Question 17

Variant 3: Glutamine

Answer 17

• Cortical areas have learned to respond more to addiction-related environmental cues
• With addiction, as activation of pleasure spikes is getting reduced, activation of craving is getting sensitized
• Reward centre shifts from the high to all the other things associated with and surrounding it.
• We want it more and actually like just wanting it
• Glutamate is excitory. Relationship of Learning and Memory to nucleus accumbent primes you to remember that excitement
• Here we see that addiction is good learning tweaked up.

Question 18

DA - VTA - NAc

Answer 18

Dopamine - Ventral Tegmental Area gives our Nucleus Accumbens a hit of pleasure
Then to…
LC + OFC = Craving
Locus Coeruleus and orbitofrontal cortex (frontal lobe) learn what we want/crave/need

which then builds…
TOLERANCE
Other results of building a tolerance are withdrawal, obsession and craving

Question 19

Progression to SUD

Answer 19

Neuroplastic changes occur at each stage of substance use development, recruiting and strengthening connections in specific areas while reducing the influence in others.

Question 20

Cognitive Deficit Model

Answer 20

• People with SUD have abnormalities in pre-frontal cortex and the signaling to mesolimbic reward system is compromised
• Drug-induced deficits are not fully reversed after stopping the substance use
• Chronic users have lower levels of GABA ( regulator of DA in VTA and NAC)
• Ex. Heroin users may already have genetically inherited PFC damage, which predisposes them to impulse control, furthering damage of chronic use and increasing the severity of the problem

Question 21

Modern Trends in Treatment and Prevention

Answer 21

1. Two themes that persist today - moral treatment - civil, respectful consideration for the recovering person
   - Asylum- supportive environment away from drinking and access to drugs
2. Detoxification - Entry into recovery but may lead to lifelong institutionalization
3. Drug Substitution - Currently, Methadone and Buprenorphine used for chronic opiate users
4. Minnesota Model of Treatment - Mainly for alcoholism - primary treatment (intensive, residential care weeks/months aiming for abstinence) - Next is a self-help group (12 steps)
5. Workplace Programs - early recognition, referral for treatment, ongoing monitoring and rehabilitation
6. Concurrent Treatment for SUD and AMI - Intensive outpatient clinics, groups
7. Monitoring of Recovery - support of recovering from several source i.e, employers, agencies etc
8. Preventative Techniques - Control sales, location, techniques, education etc