Week 4 Flashcards
Regions in the brain that are activated by substances
Basal Ganglia – motivation, habits, routines
* Repeated Exposure = ↓ sensitvity = Tolerance)
Amygdala - anxiety, irritability, and unease
* Withdrawal feelings = Motivation to seek out drug
PFC - plan, solve problems, make decisions, and exert self-control over impulses
* reduced impulsive control, not done in adolescents so at risk for substances
The structures involved in the reward system
Ventral Tegmental Area (VTA)
Nucleus Acumbens
Amygdala
Hippocampus
Prefrontal cortex
Reward system: VTA
- Dopamine-rich nucleus that mediates reward system
- Located in midbrain, next to the substantia nigra
- Sends dopamine to the nucleus accumbens, amygdala, hippocampus,and prefrontal cortex. –> START of system
- ↑ VTA pathways – implicated in OCD
Reward system: Nucelus Acumbens
Involved in all motivationally-relevant stimuli –> both rewarding or aversive.
Interface between motivation + action (connection to caudate nucleus)
Reward system: Amygdala
Happiness & Enjoyment
Anxiety, irritability, and unease - Withdrawal feelings = Motivation to seek out drug
helps you like soemthing, and not .ike something
Reward system: hippocampus
- Memory and learning
Reward system: Prefrontal cortex
Reasoning, problem-solving, impulse control, creativity, perseverance
What are the two dopamine pathways
Mesolimbic and mesocortical
Mesolimbic
route between VTA, Nucleus accumbens, and
limbic system (hippocampus & amygdala)
* Key Pathway in Pleasure and Reward.
* Substance use
EMOTIONAL aspect of wanting to use a substance again
Mesocortical
route between VTA/Nucleus accumbens and
PFC.
BEHAVIORAL aspect of going adn getting drug
What hormone is released in stress and what does it do (substance use)
cortcotropin-releasing hormone (CRH) is released
* Strengthens the Amygdala (strengthens emotional response)
* Weakens the hippocampus & prefrontal cortex (hippocampus: don’t want to remember)
You are then at greater risk for substance use:
* Negative emotional state
* Lack of executive control =↑ risk of relapse
* Memory of relief/cravings
Substance use and stress research studies
- 1/3 adol with reported abuse/neglect will develop a SUD before 18.
- 2-4x of those with PTSD developing chemical dependencies.
- SGM across lifespan = ↑ risk of TUD and AUD + homelessness = 5x
- COVID-19 = ↑ 23% increase in AUD
Is stress a universal construct?
Yes and no
Asian show more physical symptoms of stress
Americans report emotional feeling of stress
East asiains more stress with relationships
Europeans more stress around indivdiual
stuff
Neural effects of SUD
Cocaine, pathological gambling, nicotne = ↓
gray matter in PFC
Leads to hypofrontality: decreased PFC activity
–> see this in Schizophrenia
Schizophrenia:
- high comorbidites with SUD
- 70-90% nicotine dependence
- Smokers with psychiatric conditions = 34% of all
cigarette use
- AUD = 10.1%; Schizophrenia = 9.0%; together = 16%
Chicken or Egg: shchizophrenia and nictoine
Does schizophrenia cause nicotine addiction,
or does nicotine addiction cause schizophrenia
See high rates of smoking before onset, also see onset after
Does high rates of smoking before onset cause hypofrontality that we see in schizophrenia? or does hypofrontality seen in schizophrenia cause individuals with schizo. to be more susceptible to drug use
Peptides
Peptides are two or more amino acids linked by peptide bonds
Many of these are: Endogenous Opioids Receptors
Endogenous opioid receptors
Widely distributed throughout the CNS and PNS – produced by the body itself
Fxns include =
* Modulation of pain response
* Reward and reinforcement
* Inhibits flee response
Endogenous peptides vs exogenous peptides and substance use
Endogenous peptides mediate the reward and reinforcement properties
* Natural opioid receptors exist in the body
* Your body naturally produces and releases opioids to opioid receptors
Drugs of abuse/Exogenous Peptides = ↑ endorphins and enkephalins –> GIANT DOPAMINE SURGE
- Our brains are like wow that was amazing, lets do that again
CDC Guidlines for drinking
Moderate drinking not good for you, but can be made better through healthy lifestyle
Moderate drinking guidelines (CDC)
* Females = up to 1 drink per day
* Males = up to 2 drinks per day
Heavy Drinking
* Females = 8 or more per week
* Males = 15 or more per week
Binge Drinking (in 2-3 hours)
* Females = 4 or more
* males = 5 or more
Marketing of alcohol towards woman
Sugar = ↓ absorption (prolongs effects) –> drunk longer
Carbonaon = ↑ absorption –> drunk faster
Menstruation = ↓ etoh metabolism –> drunk faster
SES and alcohol
- Greatest etoh use at ends of SES ranges.
Pharmacokinetics of Ethanol
Absorption: GI Tract = 20% stomach & 80% small intestine (several variables)
Metabolism: Primarily hepatic (90%) (see next slide for details)
Excretion = Urine
* Diuretic properties –> decreased nutrients & dehydration
Intoxication = consuming etoh faster than liver can break it down
Pharmacokinetics of Ethanol: metabolism
- Metabolized by Alcohol Dehydrogenase (ADH) (requires B vitamins) –> Acetaldehyde
- Acetaldehyde (toxic, carcinogenic, prevents absorption of nutrients) metabolized by aldehyde dehydrogenase (ALDH) –> Acetate
(Approximately 36% of East Asian subjects experience an alcohol induced flush reaction d/t deficient enzyme levels of aldehyde dehydrogenase.
Thiamine deficiency
80% of ind. With AUD = Thiamine Deficiency D/T ↓ Vitamin
Absorption & ↑ Thiamine use by ADH
Reason one: alcohol dehydrogenase requires B vitamins
Reason two: alcohol impacts your ability to absorb nutrients
Neural effects of Alcohol use
OVERALL: CNS DEPRESSANT
- ETOH is an Indirect GABAA Receptors Agonist = has Sedation effect (like benzos)
–> Impairs memory functioning (hippocampus)
Over inhibition: Receptor Downregulation
- Cerebellum –> loss of coordination & consciousness
* PFC –> decreased inhibition
* Blocks Vasopressin = ↑urination & dehydration
Exception = ETOH = indirect antagonist of GABAA in the
mesolimbic pathway –> so it decreases the amount of GABA in the mesolimbic pathway, which leads to increase of serotonin and dopamine, which is why you get
addicted
Because of receptor downregulation: Withdrawal =↑ seizures
* your body doesn’t want to be in constant state of sedation, so your body has to exciite iteself more. When you take away that sedation (alcohol), you have seizures (too excited)
Wernicke-Korsakoff Syndrome
From thiamine deficiency
* Thiamine plays roles in brain cell energy production & maintenance and synthesis of myelin
Two conditions:
* Wernicke’s Encephalopathy (WE) – ACUTE phase, WILL DIE = delirium, incoordination, ataxia, decreased consciousness, memory deficits, abnormal gait
Korsakoff Psychosis – can develop after (WE) or without – CHRONIC phase = anterograde > retrograde amnesia & confabulation –> not reversible
Alcoholic Neuropathy
Nerve Damage
Alcoholic Cerebellar Damage
Deterioration of cerebellar neurons
Chronic incoordination, slurred speech, jerky movements, tremor, nystagmus
Alcoholic Myopathy
Progressive muscle damage
Symptoms include muscle atrophy, stiffness, spasms & cramps
Fetal alcohol syndrome disorders
FASD is an umbrella term for a range of
physical, cognitive, and behavioral disorders
caused by prenatal alcohol exposure
- 1-5% of 1st grade children has FASD`
Stimulant Pharmacokinetics
Stimulants impact the brain’s levels of epinephrine/norepinephrine (E/NE), dopamine (DA), and serotonin (5-HT).
* Stimulants impact each to a varying degree (selectivity).
* Cause alertness, attention, energy.
Primary risk factors:
* Reduced seizure threshold (body too excited)
* ↑ BP, HR, HTN = ↑ risk of stroke, MI
* Poor appetite, mood swings, anxiety, insomnia
* Toxic levels = paranoia, psychosis
ADHD – improvement in symptoms from medication
Fewer excitatory NTs available in their nervous system?
80% improvement in symptoms with medication
Nicotine Pharmacokinetics
Absorption
* Tobacco smoke – enters blood stream via lungs (inhalation)
* Smokeless tobacco – mucosal membrane of mouth, nose, or skin
* Reaches the brain in 7 seconds
* Mimics Ach = arousal, learning, memory, and emotions
Effects
* Binds to nicotinic receptors –> changes cerebral metabolism
* Stimulates adrenal glands –> increases BP, HR, respiration, alertness + epinephrine
Metabolism & Excretion
* ↑ metabolism in general
* Metabolized by liver, lungs, kidneys
* Excreted via urine
Endocannabinoid system
The endocannabinoid system comprises a
vast network of chemical signals and cellular
receptors that are densely packed throughout
our brains and bodies. A neuromodulation
system.
CB1 receptor –> THC
* ↑ in brain and lower conc. wide spread
* Mediates most of the psychoactive
effects of cannabinoids.
CB2 receptor –> CBD
* Principally involved in anti-inflammatory
and immunosuppressive actions.
Phytocannabinoid
biologically active compound found in
cannabis.
THC vs HEMP
THC Content = <.3% = hemp; >.3% = marijuana
Anandamide
an endocannabinoid (neuromodulator) found in the
endocannabinoid system.
- THC mimics anandamide –> effecting the endocannabinoid system.
- THC much more potent than anandamide
- Effects energy, mood, appetite, and perception of time.
Pharmacokinetics of Cannabis (Cannabinoids)
Absorption
* Inhalation – peak plasma conc. 3-10 mins; bioavailability = 10%-35%
* Oral – peak plasma conc. ~ 120 mins, bioavailability = 6%- 20%
Distribution
* Rapidly to well-vascularized organs
* Accumulates in adipose tissue
Metabolism
* Predominantly hepatic
* Able to cross the placenta; released in breast milk
* Excreted through urine, feces, and sweat.
THC Neural Effects
↓ GABA & ↑ Glutamate = ↑↑ Dopamine (Reward
System)
↑ hunger and thirst (hypothalamus
and thalamus)
↓ coordination, reaction time, and
time perception (Cerebellum)
↓ memory (hippocampus)
Body wants balance –> receptors close –> tolerance
Sugar
Glucose = primary source of fuel for the brain
* ~20% of glucose-derived energy
* Is necessary - provides precursors for NT synthesis & apoptosis
* Glucose levels correlated with thinking, memory, learning
High sugar diets = ↓ brain-derived neurotrophic factors (BDNF)
* increases risk of neurodegenerative
Should only have: 6-9 tsps
Halluciongens
2 categories
Classic (e.g., LSD, psilocybin, peyote)
* Impact serotonin
Dissociative (e.g., PCP, ketamine) – contribute to reduced control and disconnection
* Dextromethorphan (cough syrup)
* Interferes with glutamate
Technology Addiction/”Internet Gaming Disorder”
Teens aged 13-18 spent about 8.4 hours a day on screens
- “Likes”, “Re-Tweets”, “Novelty” = ↑ Mesolimbic Activation
- Need to check alerts = Compulsion?
- ↑ use = ↑ SUD, ADHD, Depression, Anxiety, poor coping
- Role of COVID-19
- Triggers = boredom, isolation, low self-esteem
