drug dependence & addiction - 1

INITIAL DRUG REWARD:
all drug of abuse increase ...

activation of dopamine receptors in the nucleus accumbens

INITIAL DRUG REWARD:
1. these nucleus accumbens neurons receive dopamine from neurons from the ...

2. this increase in synaptic dopamine can be achieved ...

1. (VTA) ventral tegmental area
2. directly or indirectly

RELATION BETWEEN ROUTE OF ADMINISTRATION & ...

addiction potential of cocaine & nicotine

EUPHORIC FOLLOWED BY DYSPHORIC FEELINGS REPORTED BY ...

individuals smoking cocaine paste

REINFORCEMENT
drugs can cause ...

reinforcement

REINFORCEMENT

reinforcement:

a process, behavior is followed by an event, this leads the action to be more likely repeated

REINFORCEMENT:

positive reinforcement: & ex.?

increasing behaviors by PRESENTING POSITIVE stimuli, such as food

REINFORCEMENT:
negative reinforcement: & ex.?

increasing behaviors by STOPPING or REDUCING NEGATIVE stimuli, such as shock

HOMEOSTASIS:
homeostasis:

set of physiological mechanisms, that serve to maintain stability of critical physiological functions

HOMEOSTASIS:

this often refers to feedback systems that occur when the ...

organism has already been thrown out of balance, but can include mechanisms to anticipate threat to the physiological balance

TOLERANCE:
drug tolerance:

a condition that occurs when the body no longer responds to a drug after chronic exposure, or a higher dose is required to achieve the same effect

TOLERANCE:
long-term drug use can lead to ... & ex.

changes in the synapses

ex. reduction in receptors affected by the drug

TOLERANCE:
tolerance builds to drugs, the same dose does not ...

give you the same effects & you need to use more to get same effect

TOLERANCE:
opiates are notorious for ...

having no absolute legal dose

TOLERANCE:
there are fewer CB1 receptors to be activated by ...

cannabinoids in long-term cannabis smokers

TOLERANCE:
tolerance occurs partly because ...

the body has a compensatory response

TOLERANCE:
when compensatory responses are present, the body ...

mounts an opposing response to minimize bodily disturbance

TOLERANCE:
pavlovian-conditioned responses:

are dependent on having the drug cues around

DEPENDENCE & WITHDRAWAL:
dependence occurs because ...

the body engages compensatory responses to counteract the effects of the drug, to attempt homeostasis

DEPENDENCE & WITHDRAWAL:
dependence ex.?

Smoking cigs makes people calm & gives them energy, withdrawal causes irritability, fatigue, insomnia, headache & difficulty concentrating

DRUG DEPENDENCE VS ADDICTION:
drug dependence:

refers to situations where the body becomes accustomed to having a drug

DRUG DEPENDENCE VS ADDICTION:
drug intake is needed to ...

prevent withdrawal symptoms

DRUG DEPENDENCE VS ADDICTION:
drug addiction:

a state in which organism engages in compulsive behavior seeking or taking drugs, even when faced w/negative consequences

DRUG DEPENDENCE VS ADDICTION:
are drug dependence & addiction the same thing?

NO!!

COMORBIDITY:
there is high co-morbidity between ...

mood, anxiety, personality disorders, & substance use problems

COMORBIDITY:
comorbidity:

refers to the presence of two or more illnesses

COMORBIDITY:
possible causes of this relationship:

alcohol drinking, fear & anxiety, genetics/prior experience

GENES INFLUENCE THE LIKELIHOOD OF ALCOHOLISM IN VARIOUS WAYS:
sons of male alcoholics
1. ...
2. ...

1. hold alcohol better
2. alcohol reduces stress for them more than usual

GENES INFLUENCE THE LIKELIHOOD OF ALCOHOLISM IN VARIOUS WAYS:
several genes related to dopamine cause ppl to be ...

more impulsive or increase craving for alcohol after the first drink

SO, WHAT HAPPENS IN ADDICTION?
one option is:
alternate option is:

physical-dependence theories of addiction

positive-incentive theories of addiction

SO, WHAT HAPPENS IN ADDICTION?
physical-dependence theories of addiction:

explain addiction as being due to developmental of tolerance & avoidance of withdrawal

SO, WHAT HAPPENS IN ADDICTION?

positive-incentive theories of addiction:

explain addiction through craving for pleasure producing effects of the drug

SEVERAL THEORIES:
list theories

1. allostasis theories
2. reinstatement & craving theories
3. decision-making theories
4. habit learning theories
5. non-disease model theories based on global allocation of reward-seeking

ALLOSTATIC THEORIES:
prolonged abstinence:

brain changes after extended drug use continue for long time, after you stop taking drugs

ALLOSTATIC THEORIES:
allostasis state: & ex.

refers to altered activity levels of primary mediators that integrate energetic behaviors in response to changing environments & challenges, such as social interactions, weather, disease

NEUROBIOLOGY OF DRUG ADDICTION: UNDER ALLOSTASIS FRAMEWORK

development of addiction caused by repeating spiral of 3 stages:

1. Preoccupation with & anticipation of obtaining & using the substance

2.Binge use & intoxication

3.Withdrawal & associated negative affect when coming down from the drug "high", which motivates future use

ALLOSTATIC THEORIES:
allostasis:

makes reward system underactive & stress system overactive, when drugs are not in body

ALLOSTATIC THEORIES:

second version of allostatic theory: normal rewards lose ability to bring pleasure

i. Glutamate from PFC accumbens is involved in reward (interacts with dopamine to make things rewarding)

ii. decreased baseline nucleus accumbens glutamate (in the absence of drug) in animals that have a history of drug intake

iii. increased PFC → nucleus accumbens glutamate response to drugs

OTHER THEORIES EMPHASIZE THE ROLE THAT CRAVING HAS ON DRUG ABUSE:
relapse after long drug-free periods suggest that ...

craving for the drug is driving force behind unhealthy use

OTHER THEORIES EMPHASIZE THE ROLE THAT CRAVING HAS ON DRUG ABUSE:
craving:

urge or desire to use the drug for its expected effects

OTHER THEORIES EMPHASIZE THE ROLE THAT CRAVING HAS ON DRUG ABUSE:
craving may be...

the motivational aspect of addiction, drug-taking is behavioral aspect

REINSTATEMENT OF CRAVING:
"craving" for drug is "reinstated" by various triggers:

animal model of reinstatement

BRAIN AREAS INVOLVED IN REINSTATEMENT:

parts of nucleus accumbens & VTA:

involved in most reinstatement

BRAIN AREAS INVOLVED IN REINSTATEMENT:

different types of reinstatement involve different neural substrates:

1. stress-induced reinstatement
2. reinstatement caused by places associated w/previous drug use

HABIT LEARNING:
drug-taking affects what system?

dopamine system

HABIT LEARNING:
dorsal striatum receives what ...

dopamine input from substantia nigra, which can alter that make habits easier to form

HABIT LEARNING:
habits:

behaviors automatically elicited by environmental stimuli

DRUG ADDICTION IS CONCEPTUALIZED AS A MALADAPTIVE ALLOCATION OF BEHAVIOR:
contingency management:

type of therapy -- pay or reward people for not using drugs

MEDICATIONS USED TO TREAT ALCOHOLISM:
antabuse (disulfiram): blocks the effects of what enzyme

acetaldehyde dehydrogenase (ALDH)

MEDICATIONS USED TO TREAT ALCOHOLISM:
enzymes in liver metabolize alcohol into ...

acetaldehyde (poisonous), but acetaldehyde is converted into harmless acetic acid by ALDH

MEDICATIONS USED TO TREAT ALCOHOLISM:
if ALDH is blocked ...

accumulation of acetaldehyde results in sickness

MEDICATIONS USED TO TREAT ALCOHOLISM:
what makes alcohol less rewarding in people w/mu opiate receptor gene?

the opiate receptor antagonist -- naltrexone

MEDICATIONS USED TO TREAT ALCOHOLISM:
naltrexone also ...

1. reduces the reward of other things in life (people stop taking it)
2. medical professionals think it should be widely prescribed

MEDICATIONS USED TO TREAT ALCOHOLISM:

what reduces withdrawal symptoms in early withdrawal?

glutamate receptor antagonist - acamprosate

REPLACEMENT THEORY:
replacement therapy:

is used to treat abuse for several drugs

REPLACEMENT THEORY:
what drugs are used to treat opiate addiction?

synthetic opiates methadone, LAAM, & buprenorphine

REPLACEMENT THEORY:
what is used to treat nicotine addiction?

nicotine patches, gums, & electronic cigs