Lecture 13 new (Pharmacology of Drugs and Abuse) Flashcards
drug abuse (substance abuse)
-maladaptive pattern of use of a substance
drug addiction (dependence)
- when an individual persists in use of alcohol or other drugs despite problems related to use of the substance
- tolerance may develop to drug
- withdrawl symptoms when use is reduced or stopped
Percent of persons 12 years of age and over with any illicit drug use in the past month
8%
Percent of high school seniors that reported nonmedical use of vicodin
1 in 10
Percent of high school seniors who have abused oxycontin in the past year
1 in 20
percent of people aged 12 or older who reported driving under the influence of alcohol at least once in the past year
-12.4%
about 31 million people
positive reinforcement
- anything that increases the probability of a behavior occuring again
- food, drugs of abuse, physical violence
reward
- positive stimuli which causes feeling of euphoria
- ex: food, drugs of abuse
Mesolimbic dopamine system
- activated by food, water, sex, drugs of abuse
- releases dopamine in the nucleus accumbens (NAcc)
Dopamine cell bodies
- located in ventral tegmental area (VTA)
- project to the nucleus accumbens, prefrontal cortex, and limbic areas
How does the administration of an abused drug change the strength of excitatory synapses on DA neurons in VTA
-increases their strength
increase in DA release at mesolimbic terminals like the NAcc (ventral striatum) results in:
-reinforcement of drug taking behavior
negative reinforcement
- removal of an aversive stimulus that increases probability of behavior occurring again
ex: if someone has a headache they take a ibuprofen. the headache is gone so negative reinforcement has occurred
physical dependence
- long-term use of drugs
- can produce tolerance and withdrawl
tolerance
- decreased sensitivity to a drug following repeated use
- ex: how many drinks to behavioral intoxication?
withdrawl
- opposite physiological effects as drug administration present during absence of use
- symptoms of withdrawal are brought to you by the body’s attempts to maintain homeostasis
heroin
- euphoria
- constipation
- relaxation
- hyperthermia
heroin withdrawal
- dysphoria
- diarrhea
- agitation
- cold-flashes (goosebumps)
negative reinforcement role in drug taking behavior
- removal of withdrawal symptoms reinforces drug use
- removal of unpleasant feelings not associated with the drug
alcohol’s reduction of social anxiety
-alcohol may be taken in advance when individual anticipates anxiogenic situations
craving
-urge to self-administer the drug even after a period of abstinence
relapse
-return to drug use after a period of drug abstinence
feelings of getting high can become associated to….
- stimuli present at the time
- stimuli associated with drug taking thus become exciting and motivated on their own and may induce drug craving
(ex: paraphernalia, location)
alcoholics in experiment with sight and sip of alcohol using an fMRI
- sip of alcohol AND sight of alcohol related images (cues) increased craving in alcoholics but not controls
- this also showed increase activation in mesolimbic dopamine system
prefrontal cortex in drug addiction
- plays an important role in executive functions
- planning
- evaluation of consequences of actions
- inhibition of inappropriate action
- prefrontal lesions cause IMPULSIVITY
Volkow (1992)
- activity of PFC of cocaine abusers during abstinence much less than normal subjects
- when performing tasks that require PFC drug addicts perform poorly compared to controls and show less PFC activation
- amount of PFC activation and weekly amound of cocaine ingestion inversely related!
maturation of PFC
- occurs around age 20
- very few addiction cases occur after the age of 20
Opiates
- derivative of morphine
- the active ingredient of juice from the opium poppy
- ingestion produceds analgesia, euphoria, relaxation
(ex: morphine, heroin, Vicodin, Oxycontin, Codeine)
Egyptians use of opiates
- medicinal value
- 1500 BCE
1914 Harrison Act
-prohibited recreational use of opiates
three major opiod receptor types
- m-opioid (MOR) receptors (analgesic and euphoric effects caused by activation)
- d opioid receptors
- k-opioid receptors
Animals lacking MOR—> what reaction of reinforcing or analgesic effects of morphine?
INSENSITIVE
MOR high in regions of brain that deal with…?
-positive reinforcement (nucleus accumbens)-analgesia (PAG, spinal cord)
Opioid Receptors
- G protein coupled
- activation leads to neuronal inhibition
cause of disinhibition by use of opiates
- inhibition of inhibitory (GABA) neurons
- this increases DA release in mesolimbic targets (gx: Nacc)
Lesion of mesolimbic dopamine system
- only decrease (not completely blocked) opiate reinforcement
- there may be other reinforcing mechanisms at work
treatment for opiate use
-methadone maintenance
methadone
- potent opiate administered orally
- low steady long lasting levels of MOR agonism in brain
- does not produce addictive high like heroin because oral administration = slow absorption
- already agonist at MOR, heroin injection is of little euphoric consequence
- most likely a life-long maintenance solution
cocain
- alkaloid dound in the leaves of the coca plant native to South America
- from 1850-1880 cocaine was a popular cure-all
- regulated by harrison narcotic act of 1914
- begining in 1970s wave of increasing cocaine use in US (IV, snorting, crack)
- 15% users—-> addicts
Freud believed which drug to treat alcoholism, depression, morphine addiction, digestive disorders, pain
COCAINE
Cocaine effects
- blocks monoamine transporters
- —> blocks the reuptake of dopamine, norepinephrine, serotonin
- it increases DA concentration in NAcc
Cocaine treatment
- no treatment to antagonize DA (dysphoria/ataxia)
- no FDA approved medications for cocaine addiction
cocaine treatment
- cocaine vaccine contains antibodies that bind to cocaine molesules and inhibit drug from crossing BB barrier
- does not stop craving
- some addicts will risk an OD by trying to take more cocaine until vaccine is saturated
- at this point the addict will die from the other effects of the drug (taking too much)
Nicotine
- active ingredient in cigarettes/chewing tabacco
- alkaloid found in the leaves of the tobacco plant native to South America
- 1500 popular in durope in pipes, cigars, chew
- mid-1800s new advances in curing tobacco leaves/ cigarette machine popularized smoking
Leading cause of preventable death in developed countries
-tobacco use
Nicotine effects
- binds to nicotinic ACh receptors (activates them_
- DA projection neurons excited/DA release increased in NAcc - ion channels open allowing Ca++ influx
6-OHDA lesions of dopaminergic pthway from VTA to NAcc
-significantly attenuate nicotine self administration
CLARIFY!!!!
Nicotine treatment
- replacement therapy with gum or transdermal patch is more effective than placebo (most successful with counseling program)
- once smoking subsided, nicotine dose can be gradually decreased
Non-nicotine component of smoking also addictive
- smokers rate the euphoria or regular or non-nicotine cigarettes in 7 seconds (less time than it takes nicotine to get to the brain)
- there may be rewarding component transferred to act of smoking after continued use
Ethanol
-most commonly used psychoactive drug in the US/most drug abused (after caffeine)
who/when was the first beer brewed?
- by the Egyptians in 3700 BCE
- 8000 BCE mead was brewed from fermented honey
American tavern
-focal point in each town for conducting business, local politics, and mail delivery
18th ammendment
- 1920
- amendment probhibiting sale, manufacture, importation, and transport of liquior
appeal of the 18th ammendment
- 1933
- repealed by congress under FDR
Regulation of alcohol today
-regulated by age, circumstance (operating a vehicle), and taxation
Effects of Ethanol
- agonist at GABAa receptors
- low doses—-> euphoria (anxiolytic
- high does—> loss of coordination, sedation
GABA agonism
- how ethanol produces sedation
- GABA A antagonists block ethanol binding site on GABA receptor preventing GABA induced sedation
Ethanol is an antagonist at….
- NMDA glutamate receptors
- non-copetitive channel blacker of the NMDA receptor (reduced Ca++ and NA+ influx)
Reduced glutamate in hippocampus leads to…
-reduced LTP and decrease declarative memory formation
NMDA receptor acitvation does what to DA neurons in VTA?
- inhibits DA neurons
- alcohol disinhibits VTA DA neurons
- leads to an overall increased DA in NAcc
ethanol treatment
-opiate antagonists reduce the rienforcing value of alcohol
naltrexone
-opiate receptor antagonist used to treat alcoholics
naltrexone symptoms in alcohol users
-increased latency to first sip
-reduced rewarding value of drinks
-reduced amount consumed
therapy—> higher success
