PS333 Exam 2

Pharmacokinetic (metabolic):

the liver may begin to synthesize more drug-metabolizing enzymes than normal when chronically exposed to a drug

pharmacodynamic tolerance

neurotransmiter receptor levels can be altered up or down depending on whether the drug acts as an agonist or antagonist

receptor levels down-regulate

Agonist

receptor levels up-regulate

Antagonist

behavioral tolerance

conditioning produces changes to the initial effects of the drug

What can cause a sudden loss of tolerance in heroin users?

Taking the drug in an unusual or novel environment

What did surveys of people with heroin use disorder reveal about non-lethal heroin overdoses?

They reported taking the near-fatal dose in an unusual circumstance or novel environment

Drug withdrawal & dependence are

interrelated

withdrawal

The negative physical and/or psychological symptoms that occur when chronic drug use is abruptly stopped

Dependence

A physiological state wherein drug discontinuation leads to an unpleasant drug-specific "withdrawal syndrome," and therefore makes someone feel like they must continue taking the drug to avoid withdrawal symptoms

the magnitude of the drug effect decreases over time— this is known as

tolerance

After a variable period of abstinence from the drug, _________ set in and improve over time

withdrawal symptoms

Physical and psychological withdrawal symptoms are ___________ and depend on a variety of factors including individual differences and extent/frequency of drug use

drug-specific

Nicotine: Drug Effects

Increased heart rate and BP
and
Increased bowel activity

Nictine: withdrawal effects

slowing of heart rate

Physical Dependence Model of Addiction:

Cessation of chronic drug use leads to unpleasant physical symptoms leading to continued drug use

Psychological Dependence Model of Addiction

Cessation of chronic drug use leads to unpleasant psychological symptoms leading to continued drug use

sensitization

some effects of a drug to increase with repeated administrations

psychoactive substances (especially psychostimulants) can activate behaviors related to motor activity

low doses (rats)

increased locomotor activity, rearing, rotation and cage climbing

psychoactive substances (esp psychostimulants) can activate behaviors related to motor activity

high doses (rats)

increased stereotyped/repetitive behaviors (head bobbing, sniffing), akin to "punding" behavior in humans (psychomotor "tics" or repetitive behaviors)

Differences between "normal" drug use and addiction

- drug "addiction" seems abnormal (compared to "normal" drug use)
- Addiction causes great personal, financial, and social harm, which many people with a SUD acknowledge
- Yet, drug use is continued despite this knowledge

cross sensitization

the use of one drug produces sensitization in the response to another drug

cross sensitzation and tolerance usually occurs when drugs are ______ class and have _______ effects

same; similar

senstization is evidence by a _____________ in the dose-response curve for motor behavior

leftward shift

_____ doses of cocaine can cause ______ sensitization responses

high ; stronger

addiction

A chronic relapsing disorder characterised by compulsive drug seeking, continued use despite harmful consquences and long lasting changes in the brain

Progression of drug use from "recreational" use to an "addictive" pattern of use

Non-problematic/recreational use, escalation of drug use, compulsive and/or problematic use, abstinence (withdrawal), relapse

Binge/intoxication:

the stage at which an individual consumes an intoxicating substance and experiences its rewarding or pleasurable effects

Withdrawal/negative affect:

the stage at which an individual experiences a negative emotional state in the absence of the substance

Preoccupation/anticipation:

the stage at which one seeks substances again after a period of abstinence

What brain structures are involved with binge/intoxication phase of "hedonic dysregulation"?

VS and BG

What brain structures are involved with withdrawal negative affect phase of "hedonic dysregulation"?

AMY and BNST

What brain structures are involved with preoccupation anticipation phase of "hedonic dysregulation"?

PFC and OFC

Key elements of addiction:

loss of control and harmful physical/social consequences associated with substance use, as well as the chronic, relapsing nature of the disorder

Match the term:
Binge intoxication

incentive salience and pathogical habits

DSM-V Diagnostic criteria for substance use disorder: criteria 1

taking the substance in larger amount or for longer tha. you meant to

Match the term:
Withdrawal negatuve affect

reward deficit and stress surfeit

Match the term:
Preoccupation antcipation

execution function deficits

DSM-V Diagnostic criteria for substance use disorder: criteria 2

wanting to cut down or stop using the substance but not managing to do so

DSM-V Diagnostic criteria for substance use disorder: criteria 3

spening a lot of time getting, using, or recovering from use of substance

DSM-V Diagnostic criteria for substance use disorder: criteria 4

craving and urges to use the substance

DSM-V Diagnostic criteria for substance use disorder: criteria 5

not managing to do what you should a home, work, or school because of substance use

DSM-V Diagnostic criteria for substance use disorder: criteria 6

continuing to use, even when it causes problems in relationships

DSM-V Diagnostic criteria for substance use disorder: criteria 7

giving up important, occupational, or recreational activities because of substance use

DSM-V Diagnostic criteria for substance use disorder: criteria 8

using substances again and again, even when it puts you in danger

DSM-V Diagnostic criteria for substance use disorder: criteria 9

continuing to use even if you have a physical or psychological problem that could have been caused or made worse by the substance

DSM-V Diagnostic criteria for substance use disorder: criteria 10

Needing more of the substances ot get the effect you want

*criteria not met if taking prescribed drugs under supervision

DSM-V Diagnostic criteria for substance use disorder: criteria 11

Development of withdrawal symptoms, which can be relieved by taking more of the substance
*criteria not met if taking prescribed drugs under supervision

DSM-V criteria for SUD: criteria 1-4

indicate impaired control

DSM-V criteria for SUD: criteria 5-7

suggest social impairment

DSM-V criteria for SUD: criteria 8-9

indicate risky use

DSM-V criteria for SUD: criteria 10-11

suggest pharmacological changes in the brain

Does the DSM-V use the word "addiction" as a diagnostic term?

No

DSM-V SUD... 2-3 symptoms =

mild severity

DSM-V SUD... 4-5 symptoms =

moderate severity

DSM-V SUD... +6 symptoms =

severe severity

Moral Theory of Addiction

- initial motivation as listed in the initiation phase
- the sign of addiction is the absence of choice the user has over the drug use.
- the user's identity and functioning are so connected with the drug that it becomes impossible for the addict to envision life without the drug.
-associated drug use with character deficits
-recovery was achieved through willpower

an early historical theory/model suggested

that addiction is the result of moral weakness

disease model of addiction

substance use leading to addiction is a biological disease resulting in physical changes in the brain that are influenced by genetic, developmental, environmental, behavioral, and social factors

Dependence model of addiction

withdrawal symptoms of a drug are so painful/distressing that individuals are willing to sacrifice almost anything to avoid withdrawal, leading to the point of SUD/addiction

The dependence model of addiction was proposed ______ understanding of brain

before

"psychological" effects have

neural basis

according to the dependence model,

People are motivated to...

avoid withdrawal

according to the dependence model,

what occurs as a result of repeated drug use?

Neurological changes

according to the dependence model, what is the basis of addiction?

Many neurological changes occur as a result of repeated drug use which are the physiological basis of psychological withdrawal, which may lead to addiction

Problems with dependence model

- some drugs that are highly addictive (e.g. cocaine) produce much less severe withdrawal
- some drugs produce withdrawal effects but are not addictive

Positive reinforcement model:

those with a substance use disorder take drugs because they enjoy their effects;

drugs are so summed, at least initially, because they are positive reinforcers;

drug seeking/taking behavior is strengthened by the positive/rewarding effects of the drug (simple associative learning), leading to addiction

Problems with Positive reinforcement model

- Tolerance to the "high" may be substantial
-Drug abuse still can occur even when reinforcers do not produce pleasure:
- Symptoms of dependence are typically not pleasurable
- Being addicted, and the social and personal losses that occur, is not desirable
- The abused drug may produce unpleasant states (self-mutilation, physical disfigurement)

When was the moral theory of addiction challenged?

in the mid-19th century during the "temperance movement"

When consumed, natural rewards (e.g. palatable food) usually result in approximately the same amount of dopamine release in brain reward centers as psychoactive drugs like amphetamines.

false

Working at McGill University back in the 1950s, Olds and Miller showed that:

rats will lever press for electrical microstimulation of the mesolimbic pathway

Addiction is conceptualized in many ways, though most definitions have several elements in common. Which of the following elements is not typically contained in definitions of addiction?

Addiction is always the direct result of drug dependence

The premise that drugs are self-administered, at least initially, because of their pleasurable effects supports which of the following models of drug addiction?

The positive reinforcement model

The Incentive Sensitization Theory of drug addiction states that feelings of “liking” the drug increase over time, while feelings of “wanting” the drug decrease over time with the development of addiction.

False

In its Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the American Psychiatric Association (APA)

avoids using the term "addiction"

According to the dependence model of drug addiction, people with a substance use disorder crave a drug because:

it will prevent withdrawal symptoms

Which of the following neural pathways is important for planning, problem solving, and learning as it relates to motivated behavior?

The mesocortical pathway

Established in 1870, the American Association for the Cure of Inebriates became the forerunner of the temperance movement. Its first principle was:

Inebriety is a disease

In 1997, the U.S. gov't took the position that drug addiction ...

is a disease

DMDA:

There are long-term neuroplastic (structural) changes that occur in the brain as a result of substance addiction

true

DMDA:

neuroplastic changes can lead to

dysregulation of brain circuits that process reward, motivation, memory, and inhibitory control

Contrary views on drug addiction as a disease

diseases are usually caused by pathogens or genetic abnormalities

brain systems controlling motivated behavior must have at least two components

activation and guidance

activation

an organism must have a need or drive (e.g. hunger or thirst) and the ability to act on that need (e.g. go foraging for food or water)

guidance

animal attraction to a specific stimulus is known as incentive; animals can also learn how to satisfy drives based on their past experiences

The mesolimbic dopamine system plays important roles in

reinforcement, motivation, and reward seeking

mesocortical system is important for

planning & learning

motor loop

Dopamine neurons in the nucleus accumbens (NAc) also send axons to the basal ganglia (BG) along with projections from the substantia nigra (SN

mesolimbic pathway

VTA to the NAc

The ventral striatum is composed of the

nucleus accumbens, ventral pallidum and medial por<on of the olfactory tubercle

The ventral striatum plays an important role in

motivation, reward and reinforcement

The Nigrostriatal Pathway

SN —> BG

What regions comprise nuclei of the basal ganglia?

The caudate-putamen and globus pallidus

The caudate-putamen and globus pallidus receive dopaminergic inputs from the

substantial nigra and nucleus accumbens

The nigrostriatal pathway is what kind of component for controlling motivated behavior

activation

The mesocortical pathway is what kind of component for controlling motivated behavior

guidance

The mesolimbic pathway is what kind of component for controlling motivated behavior

activation

Mesocortical pathway behavioral effects

short-term memories, plannings, strategies for problem solving

mesocortical pathway

VTA to the cortex (e.g. PFC), amygdala, septum, and hippocampus

Where do the cell bodies of most dopamine neurons reside in the brain?

VTA and SN