- What are some of the routes of administration? Which route of administration would get a drug to the brain the fastest? Why?
-Drugs can be administered orally, inhaled, rectal suppository, absorbed from a patch, or injected into the bloodstream, into a muscle, or into the brain
-There are fewer barriers for a drug destined for the brain if the drug is injected directly into the bloodstream.
–>Fewest barriers are encountered if a psychoactive drug is injected directly into the brain.
- Which glial cell prompts the formation of the blood-brain barrier? What kinds of substances can pass through the membranes, and which cannot?
Capillaries in most of the body allow for substances to pass between capillary cell membranes, but those in the brain, stimulated by the actions of astrocytes, form the tight junctions of the blood–brain barrier.
Molecules of these vital substances are carried in the blood to the brain and cross the blood– brain–barrier by two ways:
- Small molecules, such as oxygen and carbon dioxide, and lipid-soluble molecules can pass through the endothelial membranes.
- Complex molecules of glucose, amino acids, and other food components are carried across the membrane by active transport systems or ion pumps.
- Three regions with no blood-brain barrier were used as examples. What are they? Why do they have access to the bloodstream?
- Pineal Gland: entry of chemicals that affect day-night cycles
- Pituitary Gland: entry of chemicals that influence pituitary hormones
- Area Postrema: entry of toxic substances that induce vomiting.
- Define and provide examples of agonists and antagonists.
Agonist: A substance that enhances the function of a synapse
-Choline-rich diet increases acetylcholine (ACh)
-Black widow spider venom promotes release
-Nicotine stimulates receptors
-Physostigmine and organophosphates block inactivation
Antagonist: A substance that blocks or decreases the function of a synapse
-Botulin toxin blocks release
-Curare blocks receptors
- Define tolerance and sensitization. Does a drug always lead to one or the other, or can it lead to either?
Tolerance: Learned behavior results when a response to a stimulus weakens with repeated presentations
-Metabolic Tolerance: Increase in the number of enzymes in the liver, blood, or brain used to break down a substance
-Cellular Tolerance: Activities of brain cells adjust to minimize the effects of the substance
-Learned Tolerance: People learn to cope with being intoxicated
!!Where tolerance generally develops with repeated drug use, sensitization is more likely to develop with intermittent use!!
- Where do tolerance and sensitization happen? How do they happen?
Sensitization can be associated with increases in the number of receptors on the postsynaptic membrane, decreases in the rate of transmitter metabolism in the synaptic space, decreases in transmitter reuptake by the presynaptic membrane, and increases in the number and size of synapses.
Tolerance can result from various mechanisms, including psychological, behavioral, metabolic, neuronal, and subcellular processes
- Contrast metabolic tolerance and cellular tolerance.
-Metabolic Tolerance: Increase in the number of enzymes in the liver, blood, or brain used to break down a substance
-Cellular Tolerance: Activities of brain cells adjust to minimize the effects of the substance
- For each category of drug (cholinergic, dopaminergic, serotonergic, etc.), describe the general action of an agonist or an antagonist.
Cholinergic:
-Nicotine
-The release of dopamine provides the reinforcing aspect of nicotine.
Nicotine stimulates acetylcholine nicotinic receptors, which then indirectly causes the release of acetylcholine and several other neurotransmitters, including norepinephrine, epinephrine, arginine vasopressin, serotonin, endorphins, and dopamine.
-While smoking is a risk factor for Alzheimer disease, cholinergic agonists are medically prescribed to treat it. Acetylcholinesterase inhibitors, such as tacrine (Cognex), increase ACh levels and may provide a small benefit for people with this disease ( Birksetal., 2015).
Dopaminergic:
-Recreational use of dopamine agonists
-Cocaine, amphetamine,
methamphetamine
-Medical use of dopamine: agonists/antagonists
Dextroamphetamine (Adderall)
methylphenidate (Ritalin)
L-dopa
Chlorpromazine (Thorazine)
haloperidol (Haldol)
clozapine (Clozaril)
aripiprazole (Abilify, Aripiprex)
-The antipsychotic agent chlorpromazine (Thorazine) can lessen schizophrenia symptoms, and amphetamine or cocaine abuse can produce them. This suggests that schizophrenia may be related, at least in part, to excessive activity at the D2 receptor.
Serotonergic:
-Recreationally used serotonergics: DMT, mescaline, LSD, MDMA, psilocybin (all currently illegal for recreational use)
- Briefly summarize the three explanations for alcohol-related lapses in judgment.
- Disinhibition and impulse control:
-Alcohol has a selective depressant effect on the cortex (the region of the brain that controls judgment) while sparing subcortical structures (areas responsible for more primitive instincts, such as desire); “Too drunk to know better.”
-Impulse control is impaired after drinking alcohol because of a higher relative sensitivity of the frontal lobes to alcohol, making a person prone to risky behavior.
-Behavior under the influence of alcohol often differs with the context. - Learning:
-People who engage in polite social activity at home when consuming alcohol may become unruly and aggressive when drinking in a bar.
-Behavior under the effects of alcohol is learned.
-Learned behavior is specific to culture, group, and setting.
-Contextual cues associated with drug-taking and a drug’s nonspecific reinforcing qualities may explain some behavior under the influence, such as the violent and risky behavior associated with alcohol use.
-Negative valence
-Positive valence - Behavioral myopia:
-People under the influence of certain drugs tend to respond to a restricted set of immediate and prominent cues while ignoring more remote cues and possible consequences.
-Explains many lapses in judgment that lead to risky behavior, including aggression, and reckless driving while intoxicated.
- What are some factors that relate to the development of substance use disorder?
-Environmental factors, called adverse childhood experiences (ACEs), are associated with an increased risk of drug initiation and addiction.
-Can include emotional, physical, and
sexual abuse or neglect, among other
experiences
-Women are more likely than men to abuse nicotine, alcohol, cocaine, amphetamine, opioids, cannabinoids, caffeine, and PCP.
- In what ways are wanting and liking different?
Incentive sensitization theory:
Wanting and liking are produced by different brain systems.
-Wanting: Sensitizes with repeated drug use; craving increases
-Mesolimbic dopamine system
-Liking: Tolerance develops with repeated drug use; pleasure decreases
-Opioid neurons
- What are some approaches to treating drug abuse?
Treating drug abuse is difficult in part because legal proscriptions are irrational.
While moderate use of alcohol is likely benign, the moderate use of opioids is likely impossible.
-The two most used drugs, alcohol, and tobacco are legal.
-The drugs that carry the harshest penalties, cocaine, and heroin, are used by far fewer people.
The approaches to treating drug abuse vary depending on the drug; innovations developed during the COVID-19 pandemic impact future prevention and treatment of SUD.
