Lec 43 Addiction Flashcards
What is intoxication?
substance-specific acute syndromes associated with impaired function
What is tolerance?
reduced effect of a drug given at a constant dose [need escalating dose to get same effect]
What is sensitization?
reverse of tolerance –> increasing drug effect at constant dose
What is dependence?
altered psychological state induced by repeated exposure to a drug
–> shows withdrawal symptoms when drug is discontinued
What is addiction?
- compulsive seeking and taking of drug despite adverse consequences
What is craving?
intense urges to take a drug
What is relapse?
return to drug abuse after period of abstinence
What are the CAGE screening questions for alcohol?
- thought about cutting down
- annoyed when others criticized
- felt guilty
- eye opener
What are the AUDIT-C screening questions?
- how often do you have a drink containing alcohol
- how may standard drinks containg alcohol do you have on a typical day
- how often do you have six or more drinks on one occasion
What is reward?
positive emotional effects
What is reinforcement?
stimulus that causes reponse to be maintained and increased
positive –> increase behavior to get positive reward
negative –> increase behavior to end punishment
What is the most important brain reward circuit
the mesolimbic dopamine system
DA neurons in VTA of midbrain –> nucleus accumbens [in ventral striatum of limbic forebrain]
What is activity of VTA dopamine neurons from reward, from expectation of reward, from absence of expected reward, vs from unexpected reward?
reward: activates VTA
expectation of reward: activates VTA
absence of expected reward: inhibits VTA neurons
unexpected reward: activates neurons even more than any of the others
What is effect of drugs of abuse on mesolimbic dopamine path?
- they activate VTA-nuc accumbens
- with repeated exposure, cause changes in circuit that dampen its sensitivty –> natural rewards no longer able to activate VTA neurons, only the drug of absue powerful enough to produce effect
—-> thus pt only feels normal when drug is on board
What is role of hippocampus in drug addiction?
- involved in drug-related memories
What is role of amygdala in drug addiction?
- normally: establishes association between environmental cues and negative emotional experience = fear conditioning
- with drugs: establishes association between environmental cues and positive emotional experience of drug use
What is the role of frontal cortical regions in drug addiction?
- each area functionally connected to VTA- nucleus accumbens circuit
- their function = attention, working memory, planning, impulsivity
What is hypofrontality?
- addiction is associated with hypofunction of frontal cortical regions –> increased impulsivity and compulsivity
Which 3 drugs mimic neurotransmitters by activating receptors?
- morphine
- nicotine
- marijuana
What 2 drugs block the dopamine pump?
- cocaine
- amphetamine
What 3 drugs activate or inhibit channels?
- alcohol
- PCP
- ketamine
What is action of opiates?
- opioid receptor agonists [primarily mu]
- mimic enkephalins/endorphins/dynorphins
- inhibit inhibitory GABA neurons in VTA –> more activation of VTA DA neurons
effects: analgesia, euphoria, sedation, constipation, respiratory depression
- physical dependence and tolerance to analgesic effect can be independent from
receptor signaling = Gi
What is action of cocaine?
- blocks monamine reuptake inhibitor –> increased effect of DA [and 5HT, NE] transmission
- inhibition of DA reuptake at nucleus accumbens nerve terminals = more reward action
effects: euphoria, increased arousal/self-cofidence, decreased fatigue/appetite
repeated chronic use –> tolerance of positive effects, sensitization of adverse effects
receptor signalling = Gi and Gs
What can be used to treat opiate overdose?
- opioid receptor antagonists = naloxone, naltrexone
