Ch 32: Drugs of Abuse Flashcards
Mesolimbic Dopamine System
“reward pathway”
- a dopaminergic pathway in the brain
Note:
(this pathway connects the ventral segmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain?
THC withdrawal
- mild & short lived: restlessness, irritability, mild agitation, insomnia, nausea, cramping
other cannabinoids:
- Dronabinol: FDA approved
- Nabilone: chronic pain management
What’s opiate tolerance?
initially:
activation of the mu receptor lead to inhibition of less cAMP
Now:
up regulation of AC, increased cAMP activates cAMP response element bending protein (CREB)
- also during withdrawal the nucleus accumbens start producing dynorphin (kappa agonist)
it gets released onto the VTA
& reduces its DA release
physical dependence
“dependence”
- caused by chronic use of a tolerance-forming drug
(higher dose used, the greater the duration of use)
can cause severe withdrawal syndromes
Nucleus accumbens
promotes satiety (5-HT) and desire (DA)
may increase DA and reduce 5-HT in addiction
Prefrontal cortex
conscious component
DMT
Dimethyltryptamine (similar to 5-HT)
- hallucinogenic
Nicotine
- drug that act through ion channels
- act through nicotinergic cholinergic receptors
Psilocybin
similar to LSD & mescaline
- from psilocybin mushrooms
Sniffing
inhalation from an open container
- Impact DA transport
- prevent DA re-uptake (increasing DA at VTA targets)
physiological dependence
“addiction”
- the emotional and mental processes that’s associated with the development of and recovery from a substance use disorder/process addiction
THC effects
- presynaptic inhibition at THC receptors
- THC receptors will inhibit the release of GABA onto the VTA DA- secreting neuron
Huffing
soaking a cloth in the “stuff” prior to inhalation
cocaine:
blocks DA uptake (especially in nucleus accumbens) leads to reward effects
can be abolished in mice w/ cocaine-insensitive DA transporter
has local anesthetic effect: Blocks NA+ channels
block NE uptake
leads to increased intracranial hemorrhage, stroke, MI, seizures
note: constricts Blood Vessels (nasal damage)
Alcohol
- drug that act through ion channels
- effect GABA-A, Adenosine re-uptake, glycine receptor, NMDA receptor, 5-HT3 receptor
- dependence (6-12 hrs after cessation of heavy drinking)
- tremors, nausea, sweating, agitation, anxiety
- cause visual, tactile, auditory hallucinations
- seizures or delirium tremors (5-15% mortality)
Bagging
breathing in and out of a bad it is in
Ecstacy (MDMA)
- methylene-dioxymethamphetamine
- related to amphetamines
- cause feelings of intimacy & empathy, used in psychotherapy
- Raves
– may permanently deplete 5-HT (selective for serotonin transporter mechanism)
– acute effects: hyperthermia, dehydration, autonomic, hyperactivity, change in mental status, seizures
How do drugs of abuse activate the mesolimbic system?
- activate receptors that couple to GIO.
- activate receptors
- Impact DA transport
abuse is
“wanting together high”
Misuse is
“taking too much”
- taking more than what was prescribed
Mu opioid Drugs
- Morphine, heroine (diacetylmorphine, quickly metabolized to morphine)
- Codeine, oxycodone, meperidine (esp. in health care professionals)
- strong tolerant & dependence
- Withdrawal (dysphoria, nausea, vomiting, muscle aches, lacrimation, rhinorrhea (runny nose), mydriasis (dilated pupils), piloerection, sweating, diarrhea, yawning, fever
Inhalants
recreational exposure to nitrates, ketones, or hydrocarbons of volatile containers
(can cause white matter lesions in the CNS)
sniffing
huffing
bagging
(prevalent in children & youths)
Opiates
- knockout mice lacking mu receptor
- do not knock. out sigma or kappa
- do not show signs of dependence, analgesia or reward
- show dramatic tolerance effects to opiate addiction
- do not show physiologic effects (respiratory depression)
what causes addiction?
- feelings of euphoria & active reward systems
- repeating doses (can lead to tolerance)
- if drug can no longer be accessed, you’ll get withdrawal symptoms = DEPENDENCE
ADDICTION = when one keeps using a drug despite negative consequences
(compulsively seek/ wanting without liking)
NOT ALL USERS BECOME ABUSERS
1/6 COCAINE USERS BECOME ADDICTS
- activate receptors that couple to GIO.
- mostly at GABA receptors, causing hyperpolarization, and disinhibition (more DA release)
Tetrahydrocannabinol (THC)
- euphoria, relaxation
- well-being
- grandiosity
- altered perception
- dose dependent visual distortions (drowsiness, diminished, coordination, memory impairment)
- increased appetite
- reduced nausea
- decreased intraoccqular pressure
- relief from chronic pain
systemic administration of most drug abuse
leads to the VTA bursting with DA
LSD
Acts at 5-HT-2a receptors
- created by Albert Hoffmann
- from Ergot of Rye (1939)
- ergot produces lysergic acid
what causes a person to relapse?
re-exposure to the drug
stress
go back to a context that recalls prior drug use
LSD (Lysergic Acid Diethylamide)
- causes hallucinations
- DO NOT CAUSE DEPENDENCE/ ADDICTION
- do not increase DA release in mesolimbic structures & are NOT REWARDING
Class I drugs
- opioids (mu opioid receptor)
- Cannabinoids (cannabinoid receptor)
- Gamma Hydroxy Butyric Acid (GHB) (GABA-b)
- LSD, Mescaline, psilocybin (5-HT 2a receptor)
alcohol treatment?
- Benzos to deal w/ anxiety and agitation
- be supportive
Hippocampus
involved in memory production
it is a “good memory” of that drug participation
Mescalines
from peyote cactus
- used by native Americans & native Mexican American in rituals
- similar to LSD actions = hallucinogenic, etc.
Drugs that inhibit amine transport
cocaine
amphetamines
MDMA
why abuse drugs?
alter consciousness build body escape pleasure prevent withdrawal effects
disinhibition
- when VTA is inhibited from releasing DA
- Opiates can act at mu opioid receptors (MOR) and prevent GABA release (normally inhibits DA neurons from firing) by inhibiting Ca2+ influx or by increasing K+ conductance, & inhibiting GABA release
Amphetamines
- synthetic sympathomimetics that cause release of amines (dopamine, norepinephrine)
- inhibit storage by inhibiting vesicular monoamine transported (VMAT)
- increase in catecholamines
- increase arousal and reduce sleep
- DA increases to induce reward
- psychoses, hallucinations, & anorexic effects
drug abuse tragedies
illicit use for non-medical purposes
Amygala
adds an agreeable/disagreeable nature to an event
may add to the “it was good” nature of drug participation
GHB effects
- acts as GABA-b receptors on both pre-synaptic cell and VTA DA-secreting neurons
- the presynaptic GABA neurons are more sensitive to GHB = overall effect seems to be in favor of disinhibition of the pre-synaptic cell release of GABA
Ergotism
- convulsive ergotism includes: shakiness, tremor, convulsions, hallucination
- (witchcraft??) –> Salem witch trials?
Ketamine & PCP
- drug that act through ion channels
- develop as general anesthetics (induce anesthesia)
- act as NMDA receptors
- neither are addictive, BUT can be psychedelics
- chronic use can lead to schizophrenia-like psychosis
PCP –> “angel dust”
Ketamine –> “special K”
(both are white, crystalline powders, can be sold as liquid, capsules, pills, and can be snorted, ingested, injected, and smoked)
Ventral Tegmental Area (VTA) protects to:
Nucleus accumbens
Amygala
Hippocampus
Prefrontal cortex
(mostly DA/dopamine releasing neurons)
- activate receptors
- open ion channels to cause disinhibition or excitation (more DA release)
what happens when VTA start releasing DA?
- once DA is released, it starts bursting onto other sites
- leads to an “award” (press a lever so it can happen again)
Cocaine
- from Erythroxylon coca in Andes
- water soluble (in hydrochloride form)
injected or absorbed in mucosa
- water soluble (in hydrochloride form)
– when heated in alkaline solution= becomes free base
can be smoked
Benzodiazepines
- drug that act through ion channels
- act at GABA-a receptors
- withdrawal effects last just a few days
