addiction day Flashcards
Neurobiology of Addiction
- Addiction is a chronic, progressive behavioral disorder whose central feature is compulsive drug use despite adverse consequences
- Addiction pathophysiology involves the brain reward system and the alterations that reward enhancing drugs effect on this system
Ventral Tegmental Area (VTA)
Location of dopamine cell bodies that projects to nucleus accumbens (reward center) and prefrontal cortex (executive control)
Nucleus Accumbens (NA)
- The “reward center” of the brain.
- Integrates VTA (dopamine) and PFC (glutamate) inputs to determine motivational output.
- Incentive (appetitive)
- Reward (consummatory)
Prefrontal Cortex (PFC)
- Exerts executive control over midbrain structures
- Judgment
- Cost-benefit analysis
- Consider Further PFC delineation next
With increasing addiction, frontal lobe structures can become
less active (less glutamate) and even atrophy allowing increasing, maladaptive addictive (more DA) behaviors to occur. (risk calculations are in error, emotional valence is put onto the addictive substance and response prevention falters
DLPFC-=
statistical analysis, prioritizing, top down control center:(failure to assess the risks of a behavior ie drunk driving)
VMPFC=
assigns emotional valience (drinking feels good, less stress, more social)
OFC-
impulse prevention ( I can beat up that football player, grope that model, drive my car)
ACC=
vigilance(Scanning environment for next beer, vodka, bar…)
Decision Making is
Glutamate Driven via PFC structures
Limbic Drive is
Dopamine Driven
D3 receptors govern
static levels of DA neuronal activity to allow homeostatic wakefulness, alertness, etc
D2 receptors are
pulsatile depending on motivation, drive, reward expectations
Effects of Drugs and ‘Addictive Behavior’ on the Brain Reward Pathways
1. All act in brain limbic reward pathways to either: enhance dopamine (DA) release enhance DA effects in the Nucleus Accumbens (Nac) or related structures or produce effects similar to DA 2. Drug-induced states are important motivators/reinforces of initial drug use 3. Chronic use leads to reward circuitry changes that promote more future drug use - Increased limbic function - Decreased PFC function
The VTA barn supplies DA to
the nucleus accumbens (NAc)
The Amygdala assigns a
pleasure, threat, or an emotional value to the linkage between 1 and 2 (perhaps this is the terrain of the ranch or how much the horses are to be fed?)
1-3 are the Limbic Addiction Pathways that are excessive in addictive behaviors
With increasing addiction, frontal lobe structures can become
less active (less glutamate) and even atrophy allowing increasing, maladaptive addictive (more DA) behaviors to occur. (risk calculations are in error, emotional valence is put onto the addictive substance and response prevention falters
Summary
- Must know the neurotransmitters involved in normal reward and addiction (DA/GLU)
- Must know functional brain areas
- Must know if areas become more or less active with addiction
alcohol binds to
GABA-A receptor
Intoxication/Withdrawal Alcohol
- Anxiolysis
- Disinhibition
- Slurred Speech
- Ataxia
- Sedation/Stupor
- Respiratory Supression
- Coma
- Death
Rx with support, restraint, protect airway, ventilate
alcohol withdrawal
- Agitation, Insomnia
- Tremor
- GI upset
- Inc Pulse, HR, BP
- Seizures
- Hallucinations
- Delirium
- Death
Rx with benzodiazepines (cross reactive) until vital signs and withdrawal symptoms normalize
Intoxication/Withdrawal Sedatives (Benzodiazepines, Barbiturates)
- Anxiolysis
- Slurred Speech
- Ataxia
- Sedation/Stupor
- Respiratory Supression
- Coma
- Death
Rx with support, restraint, protect airway, ventilate
Reverse with flumazenil
For benzodiazepines
Will not work for alcohol or barbiturates
withdrawal symptoms with benzo and barbs
- Agitation, Insomnia
- Tremor
- GI cramps
- Hypereflexia
- Inc HR
- Seizures
- Hallucinations
- Delirium
- Death
Rx with benzodiazepine replacement until vital signs and withdrawal symptoms normalize
Stimulants and the D2 ReceptorCocaine, Amphetamine
- Stimulants block dopamine reuptake, may reverse it
2. The net effect is more DA availability in the mesolimbic system which allows increased CNS arousal and excitability
Intoxication of Stimulants
- Elevated mood and esteem
- irritability
- Insomnia
- Appetite loss
- Dilated pupils
- Racing heart
- Inc BP, elevated temp
- Hyperreflexia
- Psychosis
- Cardiac arrest
- seizure
Rx with support, and use meds to reverse specific intoxication symptoms
withdrawal of stimulants
- Fatigue
- Anhedonia
- Depression
- Increased sleep
- Increased appetite
Opiates and the Opioid System
- affect mu, delta, kappa receptors
2. many prescription narcotic pain meds are naturally occurring alkaloids (poppy), some are synthetic
Mu (OP3,MOP) reduces
pain, increases positive emotion,
Rx opiates are often
full agonists and very effective at activating endogenious opioid receptors
Kappa(OP2, KOP)/delta(OP1, DOP) allows
mild analgesia
They are g protein linked and cause neuronal hyperpolarization via
cAMP reduction and increased K+ influx and decrease Ca++ efflux –> Increases descending midbrain pain inhibitory paths
Next increasing serotonin and enkephalin firing
Many prescription narcotic pain meds are naturally occurring alkaloids (poppy), some are synthetic
- Morphine, codeine,oxycodone, hydrocodone, tramadol
- They tend to activate the Mu, OP3, MOP receptors to control pain and improve the emotional state associated with said pain
Intoxication of Opiates
- Elevated mood
- Pupil constriction
- Respiratory suppression
- Gag reflex loss
- Low HR, BP
- Constipation
Rx with support, protect airway and use naloxone to reverse
dopamine lives in
ventral tegmental area (VTA) –> location of dopamine cell bodies that project to nucleus accumbens (reward center)
prefrontal cortex does
- judgement
- cost-benefit analysis
- exert executive decision
dorsal lateral prefrontal cortex
does statistical analysis, prioritizing, top down control center (failure to assess the risks of a behavior –> drunk driving)
ventral medial prefrontal cortex (VMPFC)
assigns emotional valience (drinking feels good, less stress, more social)
orbital frontal cortex (OFC)
impulse prevention (drinking and driving is bad) –> but for addictive pts have cold OFC
ant. cingulate (ACC)
vigilance (in ADHD you get light up all over not just ACC)
Hallucinogens
Phencyclidine (PCP), lysergic acid (LSD), mescaline, peyote, psilocybin
Treatment is supportive
intoxication of hallucinogens
Intoxication=
- Perceptual distortion
- Hallucinations
- Depersonalization
- Nystagmus
- Tremors
- Hyperreflexia
- Racing heart
- Flashbacks
- Paranoia
Cannabis
Intoxication=
- Elevated mood
- Expansive thought
- Sedation
- Pupil constriction
- Red conjunctiva
- Increased appetite
- Panic
- Paranoia
Stages
- Precontemplation
- Contemplation
- Preparation
- Action
- Maintenance
Precontemplation to Contemplation
- Consciousness raising
- Emotional arousal/Dramatic release
- Social liberation/Environmental reevaluation
Contemplation to Preparation
Self-reevaluation
Preparation to Action
Self-liberation/Commitment
Action to Maintenance
- Countering/Counterconditioning
- Environmental control
- Rewards
- Helping relationships
chloride ion goes into
GABA-A receptor
intoxication is always the opposite of
withdrawal
gaba must be bound to GABA receptor
in order for benzo to work
alcohol withdrwal
- delirium tremor (can’t remember about any exp)
- hallucinations (doc, I saw the strangest thing!)
- -> usually visual hallucination
lorazepam is the DOC for alcohol withdrwal ??? (check with the lecture audio)
b/c no worries about liver failure
what are the two addictive stimulants and the D2 receptor?
cocaine, amphetamine
stimulants block dopamine
reuptake, may reserve it
the result of stimulants such as cocaine and amphetamine are
the net effect of more DA availability in the mesolimbic system (positive symptoms for shcizo) which allows increased CNS arousal and excitability
intoxication of cocaine lead to
by blocking the reuptake of neurotransmitter leading to
- elevated mood and esteem
- irritability
- insomnia
- appetite loss
- dilated pupils
- cardiac arrest –> can lead to death
- seizure
- causes vasospasm
withdrawal of stimulants (cocaine and amphetamine)?
- anhedonia
- depression
- increased sleep
- increased appetite
- fatigue
trazodone and clonidine
prevent the sleeping withdrawal effect
what opiate receptor is responsible for reducing pain, and feeling good (positive emotion)?
Mu
what are some intoxication symptoms of opiates?
- elevated mood
- pupil constriction
- resp. suppression
- loss of gag reflex
- constipation
what are the withdrawal symptoms of opiates?
- restless
- watery eyes
- yawning
- dilated pupils
- muscle cramps
- agitation –> probably the most important withdrawal symptom
- goose flesh, lacrimating
what are some of the drugs that are hallucinogens?
- phencyclidine (PCP)
2. lysergic acid (LSD)
what are some of the intoxication symptoms of hallucinogens such as PCP and LSD?
- perceptual distortion
- hallucinations
- depersonalization
- nystagmus
- tremors
the only drug that causes vertical nystagmus
PCP
intoxication of cannabis
- elevated mood
- red conjunctiva
- pupil constriction
what is harm reduction?
to make the drug intake safer and healthier
stages?
precontemplation –> contemplation –> preparation –> action –> maintenance
what is the characteristic of contemplation to preparation?
self-reevalution
prep to action?
self-liberation/commitment
what are action to maintenance
- countering/counterconditioning
- environmental control
- rewards
- helping relationships
what is precontemplation?
unaware of the problem
what is contemplation?
aware of the problem but ambivalent about action
what is preparation?
first decision to change –> small steps taken
what is action?
change begins –> trial and error
what is maintenance?
new behaviors practiced –> focus on relpase prevention
Harm reduction
Replace harmful inhaled tobacco smoke with nicotine (full agonist is replaced with full agonist)
Prevents withdrawal
Easier withdrawal
Avg cigarette has 1.1 mg nicotine, cigar 20 mg…
Side effects similar to smoking too many cigarettes at once (activating)
? E-cigarette use
Used like a patch to detox
Used like methadone maintenance to avoid withdrawal
Data hinting that this may not be helpful…
Antidepressant Bupropion SR Mechanism for Smoking Cessation
Blocks neuronal reuptake/recycling of NE and DA
Generally this improves alertness, attention, concentration, motivation…
The twice daily Slow Release (SR) product is also approved for
smoking cessation
By blocking Dopamine (DA) and Norepinephrine (NE) transporters, these transmitters build up in synapses and activate neurons in the area.
This may desensitize DA reward circuitry so cigarette based activation is not missed by the patient
This may provide alertness, energy, better cognition and mood so that cigarette effects are not missed
A partial nicotine receptor agonist
Replace a full agonist (nicotine) with a partial agonist
Varenicline
- Instead of full nicotine agonism and reward pathway firing,
- Varenicline does this partially allowing this system to be active, avoid most withdrawal
- And provide some of the benefits of nicotine use without the harm
Chronic use leads to reward circuitry changes that promote more future drug use
- Increased limbic function
2. Decreased PFC function
The Amygdala assigns
a pleasure, threat, or an emotional value to the linkage between 1 and 2 (perhaps this is the terrain of the ranch or how much the horses are to be fed?)
The VTA barn supplies DA to
the nucleus accumbens (NAc)
With increasing addiction, frontal lobe structures can become
less active (less glutamate) and even atrophy allowing increasing, maladaptive addictive (more DA) behaviors to occur. (risk calculations are in error, emotional valence is put onto the addictive substance and response prevention falters
