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20 Cards in this Set

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What are the TWO KEY DETERMINANTS TO A SUBSTANCE EPIDEMIC?
Decreased perceived risk AND availability/supply.
What is the addiction cycle?
DRUG USE --> EUPHORIA (POSITIVE REINFORCEMENT) --> NEUROADAPTATIONS from chronic use --> CRAVING (NEGATIVE REINFORCEMENT) --> Drug use.

Drug use/euphoria and salience ALL INCREASE DOPAMINE RELEASE AND D2 BINDING AND INCREASED GLUTAMATE.


Base-line craving both DECREASE DA AND GLUTAMATE.

Drug-induced craving (withdrawal) involves DECREASE IN GLUTAMATE.

CUE-INDUCED CRAVING INCREASES DA/GLU
What is the DA system?

MESOCORTICOLIMBIC!
Starts in the VTA of thalamus. Connects to the hippocampus (memories attached to brain reward), nucleus accumens, prefrontal cortex.
What are TOXIC EFFECTS OF COCAINE USE?
Think stimulant side effects. Hypertension, cardiac arrythmias, seizures, MI/strokes/vasospasm leading to ischemia/necrosis
What are other problems with cocaine use?
Heart issues(MI/CVA/angina/arrythmia/vasospasm/cardiomyopathy,myocarditis).

Pregnancy issues - interferes with pregnancy.

Hyperpyrexia.

Renal failure.

Perforated nasal septum.
If you a young person comes in with REAL (not perceived) cardiac problems with no risk factors, think?
STIMULANTS (PRIMARILY COCAINE)
What is bad about cocaine and alcohol mixing?
Cocaethylene is a metabolic by-product. can be cardiotoxic and psychoactive. reduced anxiety.
What is a speedball?
Heroin/cocaine together. Increases DA in Nuc.Acc. by 1000%. Decreases negative symptoms of cocaine.
Compare amphetamines and cocaine.
Amphetamines can have longer half-lives, more euphoria. MORE NEUROTOXICITY THAN COCAINE.
Mechanism of action of cocaine (and methylphenidate - ritalin)
DOPAMINE REUPTAKE INHIBITOR by BINDING TO DAT (DA TRANSPORTER)
What neurotransmitters does the VTA release? where to?
Among others (?), VTA releases DA and GLU to Nuc.Acc.
Mechanism of action of amphetamine?
DA DUMP!
What is a commonality between drugs of abuse and DA levels in Nuc.Acc?
Drugs of abuse INCREASE DOPAMINE LEVELS IN NUC.ACC.
What are the two major areas of the limbic system activated by cue-induced cravings?
Anterior Cingulate Gyrus, Amygdala.

Test these regions for activity when testing anti-craving medications.
What peptides are released in response to stress?
INCREASED CRF AND NOREPI.

Would NOREPI/CRF antagonists be effective in reducing stress-induced cravings?

Stress in cocaine treated animals only releases DA. Stress normally releases DA via GLU that is mediated by CRF increase.
What are the neuroadaptations to cocaine use?
Depletion of DA and GLU. Hedonic dysregulation.

GABA/dynorphin UPREGULATION.
What are cocaine withdrawal symptoms? life-threatening?
Opposite of stimulant effects. Depression, bradycardia, hyperphagia, motor problems.

NOT LIFE THREATENING.

Severity of withdrawal symptoms indicate worsening of prognosis.
What is significance of hypofrontality in addiction?
PFC is hypometabolic at baseline in dependent patients. Becomes hypermetabolic during cue-induced craving. PFC involved in conflict registration, behavioral inhibition, motivation, executive function.

DENIAL?? PFC DYSFUNCTION!
What area of the brain is involved with denial?
PFC! DENIAL IS HALLMARK!
What are best therapies? Are vouchers effective?
Best therapy looks like Individual counseling. CBT and other psychotherapies can be effective.

Vouchers are effective long-term, but patients return to using once reward is no longer offered.

NO MEDICATIONS PROVEN