Chapter 6 Flashcards
Psychopharmacology
Study of the ways drugs affect the nervous system and behavior
Psychoactive Drug
Substance that acts to alter mood, thought, or behavior, used to manage neuropsychological illness
Often used recreationally
Drugs
Chemical compounds administered to produce a desired change
Improvement of physical/mental symptomatology
Routes of Drug administration
Orally → safest and most convenient: ingestion » absorption by stomach/small intestine » then enters bloodstream (water-soluble)
Inhaled → encounter few barriers enroute to the brain » absorbed into bloodstream almost immediately
Injected into bloodstream → fewest barriers to brain but must be HYDROPHILIC » dosage can be reduced by factor of 10
Injected into muscle → encounter more barriers than inhaled drugs
Injected into brain → acts quickly and in LOW doses
Absorbed through skin → adhesive patches into bloodstream » small-molecule drugs can penetrate
Weak acid drugs
Pass from stomach into bloodstream
Weak base drugs
Pass from intestines to bloodstream
Factor of 10 rule
1 milligram of amphetamine produces noticeable behavior change orally
If inhaled into lungs or injected into blood, a dose of 100 ug yields the same results
If amphetamine is injected into CSF, 10 ug is enough for identical outcome
1 ug if drug directly applied to target neurons
Blood-brain barrier
Cell membranes, capillary walls, and placenta → all barriers to internal movement of drugs
Blood-brain barrier prevents most substances from entering brain via the bloodstream
Protects brains ionic balance
Denies neurochemicals that can disrupt neural communication
Protects brain from circulating hormones and from toxins/infectious diseases
Endothelial cells → blood-brain barrier
Form a cell layer that lines blood vessels → regulates exchanges between bloodstream and surrounding tissues
Endothelial cells in capillaries throughout the body are not tightly joined: easy for substances to move in and out of the bloodstream
Endothelial cell walls in brain are fused to form fight junctions → most substances cannot squeeze between them
Barrier-free Brain sites
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
What helps access and support brain function?
Brain needs oxygen and glucose for fuel and amino acids to build proteins
Fuel molecules reach brain cells from blood, carbon dioxide + other waste products are excreted from brain cells and carried away by the blood
Molecules of these vital substances cross the blood-brain barrier in 2 ways:
↳small, uncharged molecules (ex. Oxygen and carbon dioxide) are fat soluble and can freely 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
SOME psychoactive drugs (must be small or have correct chemical structure) DO gain access to the CNS
How body eliminates drugs
Drugs are catabolized in the kidneys, liver, and intestines → then excreted in urine, feces, sweat, breast milk, and exhaled air
Liver is active in catabolizing drugs: houses a family of enzymes involved in drug catabolism
The cytochrome P450 enzyme is involved in drug catabolism → some of which are also present in gastrointestinal tract microbiome
Liver is capable of turning drugs into other forms that are more easily excreted from body
Agonist vs. Antagonist drugs
Agonist → drugs that increase neurotransmission
Antagonist→ drugs that block; decrease neurotransmission
Drugs and Major steps in neurotransmission
Drugs can influence synthesis of NT, packaging and storage of NT, release of NT, receptor interaction with the NT, and reuptake/degradation of the NT
Tolerance to drugs → 3 types
Decreased response to a drug with repeated exposure → 3 types
Metabolic tolerance: increase in number of enzymes in liver, blood, or brain used to break down a substance → metabolized faster = blood levels decrease
Cellular tolerance: activities of brain cells adjust to minimize effects of substance → accounts for low signs of intoxication with high blood-alcohol levels
Learned tolerance: People learn to cope with being intoxicated so they may no longer appear intoxicated
Sensitization relative to drugs
Sensitization more likely to develop with periodic use → occasional drug taker may have an increased responsiveness to successive, equal doses
Related to dependence→ before a person becomes dependent they must be sensitized by numerous experiences with the drug
Life experiences (stress) can produce effects resembling sensitization that prime nervous system for addiction
Sensitization to SSRI’s causes them to work → must be taken for several weeks first
Psychoactive drugs
Psychoactive drugs can be grouped based on the primary neurotransmitter system that they are known to effect
Priming
Synapse first receives chemical then becomes more ready to fire after first dose
Main psychoactive drugs → 9 types
Adenosinergic antagonist → caffeine
Cholinergic agonist → nicotine or diazepam, alprazolam, clonazepam
Glutamatergic antagonists → ketamine/PCP or memantine
Dopaminergic antagonists → Thorazine, Haldol, clozaril
Dopaminergic agonists → cocaine, amphetamine, methamphetamine, or aderall, Ritalin etc.
Serotonergic agonists → DMT, ecstasy, LSD or Zoloft, Prozac, tofranil
Opiodergic agonists → opium, morphine, heroin, or codeine, oxycodone,fentanyl
Cannabinergic agonists → THC
Adenosinergic antagonist
Most widely consumed psychoactive drug: caffeine
Binds to adenosine receptors without activating them → suppresses endogenous adenosine which includes drowsiness → leads to alertness
Also inhibits enzyme that usually breaks down the second messenger; cyclic adenosine monophosphate (cAMP): resulting increase in cAMP leads to increased glucose production→ resulting in more available energy and higher rates of cellular activity
Promotes release of dopamine and acetylcholine
Repeated daily use: mild form of drug dependence → fade within a week of abstinence
Cholinergic agonist
Nicotine→ feelings of relaxation, sharpness, calmness, and alertness
Within a few seconds from inhalation, nicotine stimulates acetylcholine nicotinic receptors
Acetylcholine nicotinic receptors cause the release of acetylcholine, norepinephrine, epinephrine, serotonin, endorphins, and dopamine
At low doses can act as a stimulant→ very high doses: dampens neuronal activity
Dependence involves both psychological and physical aspects
Potentially lethal poison → smoking can be a risk factor for Alzheimer’s disease
GABAergic agonists
Alcohol
At low doses: reduce anxiety, medium doses: sedate, at high doses: they anesthetize or induce coma → death
GABAa receptor contains a binding site for GABA, one for alcohol, and one for benzodiazepines and a Cl-
Excitation of the GABAa receptor produces an influx of Cl- through its pore → influx of Cl- increases concentration of negative charges inside the cell membrane, hyperpolarizing it (less likely to propagate an AP) → widespread reduction of neuronal firing underlies the behavioral effects of drugs that affect GABAa synapse
Summation in GABAergic agonists
Sedative-hypnotic drugs (alcohol) increase GABA binding, thereby maximizing the time the pore is open
Antianxiety drugs (benzodiazepines) influence the frequency of pore opening
Because actions summate, they should not be taken together
Cross tolerance for benzos and alcohol→ act on NS in similar ways
GABAergic Receptors
Alcohol consumption has short-term psychological and physiological effects that depend on: alcohol volume, body mass, food intake, genetics, etc.
Small amounts improve mood, sociability, fine muscle coordination, etc.
Medium doses result in lethargy, sedation, lack of balance, etc.
Long-term and frequent consumption can lead to increased risk of alcoholism → results in damage to central and peripheral nervous systems, as well as nearly every other system and organ in the body
Glutamatergic antagonists
Glutamatergic system has several receptors: NMDA, AMPA, and kainite
Antagonists for NMDA receptor such as phencyclidine (angel dust) and ketamine can produce hallucinations
Both PCP and ketamine are known as dissociative anesthetics → compounds that produce feelings of detachment and dissociation from environment and self (distort perceptions of sight and sound)
Ketamine is currently medically prescribed for starting and maintaining anesthesia
Dopaminergic Antagonist vs. Agonist uses
DA agonists used recreationally→ cocaine, amphetamine, methamphetamine
DA agonists used medically → dextroamphetamine (Adderall), methylphenidate (Ritalin) , L-dopa
DA antagonists used medically → for treatment of schizophrenia: chlorpromazine (Thorazine)
Dopamine agonists
Cocaine→ from coca plant
Amphetamine increases dopamine in the synaptic cleft by reversing the dopamine transporter→ also reverse transporter that packages DA in vesicles (instead takes packaged dopamine and releases it into terminal)→ reverses transport to presynaptic cell = more DA
Cocaine ALSO blocks the Reuptake (more DA in synapse)
Amphetamine (Adderall) and methylphenidate (Ritalin) medically prescribed to treat ADHD → recreational dose is 5OX stronger than clinical dose
Dopamine antagonists
Use of dopamine antagonist drugs that preferentially bind to D2 receptors improved functioning of people with schizophrenia
Schizophrenia hypothesis: excessive frontal lobe DA activity → therapeutic actions of D2 antagonists are not fully understood
Serotonergic agonists
Natural recreationally used serotonergics: mescaline (peyote), DMT, and psilocybin
Synthetic rec serotonergics: LSD, and MDMA (ecstasy/Molly)
Some serotonergic agonists prescribed to treat major depression:
Monoamine oxidase (MAO) inhibitor → drug that blocks MAO enzyme from degrading NT such as: 5-HT, NE, and DA
Tricyclic antidepressants → Drug characterized by its 3-ring chemical structure which blocks 5-HT reuptake transporter proteins
Selective-serotonin reuptake inhibitor (SSRI)→ drug that blocks 5-HT Reuptake into the presynaptic terminal and is MOST commonly used to treat depression
Drug effects at 5-HT receptors
MAO inhibitor (agonist) inhibits the breakdown of serotonin = more serotonin available for release
SSRI (agonist) and tricyclics (agonist) block transporter protein for serotonin Reuptake = serotonin stays in synaptic cleft for longer
Both increase availability of 5-HT differently
Opioids
Opioid: any endogenous or exogenous compound that binds to opioid receptors to produce morphine-like effects → narcotic (sleep inducing) and analgesic (pain-relieving) properties
3 sources of opioids
Isolated → morphine, codeine
Altered → heroin, oxycodone
Synthetic →fentanyl and methadone
Opiodergic agonists
Semi-synthetic: heroin and oxycodone → heroin is much more potent than morphine and penetrates blood-brain barrier faster
Alter pain perception, relaxation, and can lead to euphoria
Can lead to respiratory depression: high tolerance = higher dosage = resp. dep. → chest cavity stops breathing + coughing functions → suffocation
Repeated opioid use produces a tolerance that effective dosage may increase tenfold within few weeks → brutal withdrawl symptoms
Naloxone (Narcan) → opiodergic overdose
Opioid use results in both tolerance and sensitization, an opioid user is at constant risk of overdosing
Narcan/naloxone act as antagonists at opioid receptors
Competitive inhibitor → acts quickly to block opioid action by competing with the opioid for binding sites → reverses AP
Cannabinergic agonist
Tetrahydrocannabinol (THC) is one of 84 cannabinoids and is main psychoactive constituent in cannabis
THC alters mood by interacting with cannabidiol 1 (CB1) receptor found on neurons, and also binds with CB2 receptors found on glial cells and in other body tissues
Cannabis has extremely LOW toxicity (no OD)
May cause physiological and psychological dependence
Cannabinergic uses
Usefulness of THC and CBD as therapeutic agents:
Substitute for opioids
Treat glaucoma
Eating disorder treatment
Chronic pain treatment
Disinhibition Theory
Alcohol has a selective depressant effect on the cortex → region that controls judgment
Limitation: behavior under influence of alcohol often differs with context→ behavior under influence of alcohol is learned (specific to culture, group, and setting)
Behavioral myopia
Under influence of alcohol people respond to a restricted set of immediate and prominent cues and ignore more remote cues and potential consequences
Not see past immediate reward/urge → lack of foresight
Substance abuse
Pattern of drug use in which people rely on a drug chronically and excessively allowing it to occupy a central place in their life
Drug pattern is well established
Addiction
Brain disorder characterized by escalation, compulsive drug taking, and relapse
Called substance use disorder per the DSM-5
Psychomotor activation
Increased behavioral and cognitive activity so that at certain levels of consumption, the drug user feels energetic and in control
Abused drugs act on the same target: dopaminergic pathway
↳ from ventral tegmental area to nucleus accumbens
Drugs increase dopamine activity in the nucleus accumbens (directly or not)
Drugs that decrease abuse → decrease dopamine activity in the nucleus accumbens
Risk factors in addiction
Adverse childhood experiences (ACE’s) are associated with an increased risk of drug initiation and addiction
Can include emotional, physical and sexual abuse or neglect among other experiences
Wanting-and-liking theory
Aka incentive sensitization theory
Wanting (craving) and liking (pleasure) may be produced in different parts of the brain
Wanting: sensitized with repeated drug use; craving increases → mesolimbic dopamine system
Liking: tolerance develops with repeated drug use; pleasure decreases
Cue reactivity
Increased use leads to an association of cues→ any instruments associated with drug use can cause desire to increase: relapse
Paraphernalia increases feelings associated with drug use → classical conditioning
Neural basis of addiction
Decision to take drug → frontal cortex
Drug then activates endogenous opioid systems (related to pleasurable experiences)
Wanting drugs → from activity in nucleus accumbens in dopaminergic system
Mesolimbic pathways → addiction
Axons of dopamine neurons in midbrain project to the basal ganglia, frontal cortex, and allocortex
Drug cues release DA in this system → triggering a wanting response and repetitive benaviors
Cue + drug taking creates neural associations in the dorsal striatum (basal ganglia)→ leads to loss of voluntary control and increased craving
Drugs + Brain damage → general
Natural substances such as glutamate can be neurotoxins → become toxic over time due to excess buildup in brain
Hard to determine whether recreational drugs are harmful:
Drug itself? Or factors associated with drug use?
Do drugs initiate problems? Or just aggravate preexisting conditions?
Hard to isolate cause-and-effect
Brain damage + Alcohol
Chronic alcohol use can be associated with damage to the thalamus and limbic system
Alcoholics typically obtain low amounts of thiamine (vitamin B1)
Thiamine plays a vital role in maintaining cell membrane structure → can lead to severe memory loss problems and pathological lying
Brain damage + cocaine
Related to the blockage of cerebral blood flow and other changes in blood circulation
Brain imaging studies suggest that cocaine use can be toxic to neurons
Brain damage + marijuana
Plant contains at least 400 chemicals
Determining whether a psychotic attack is related to THC or to some other chemical in marijuana is almost impossible
Hormones
Secreted by glands in body and by brain
Brain + body hormones that interact form feedback loops that regulate their activity
Hormonal influences change across lifespan → influences development and body/brain function
Hormone systems are like NT activating systems: use bloodstream as a conveyance→ epinephrine is used in hormone form in fight-or-flight response
Hierarchical Control of hormones
Hypothalamus → produces neurohormones to stimulate pituitary gland
Pituitary gland → secretes releasing hormones to influence target endocrine glands
Target endocrine glands → release appropriate hormones into the blood to act on target organs and tissues
Steroid hormone
Fat-soluble chemical messenger synthesized from cholesterol
Bind to steroid receptors on the cell membrane and influence DNA transcription
Examples: gonadal (sex) hormones, thyroid, cortisol
Peptide hormone
Chemical messenger synthesized by cellular DNA ‘ that acts to affect the target cells physiology
Binds to metabotropic receptors → leads to cascade effects
Examples: insulin, growth hormone
Functional groups of hormones → 3
Homeostatic hormones: maintain internal metabolic balance and regulation of physiological systems
Gonadal (sex) hormones: control reproductive functions, sexual development, and behavior
Glucocorticoids: secreted in times of stress; important in protein and carbohydrate metabolism
Homeostatic hormones
Homeostasis of intra and extracellular environments is essential → body must stay within certain biological parameters for effective functioning
Diabetes mellitus → failure of pancreas to secrete enough insulin which leads to impaired functioning
Anabolic-androgenic steroids
Class of synthetic hormones related to the male sex hormone testosterone that have both muscle-building (anabolic) and masculinizing (androgenic) effects
Health risks:
Body reduces production of testosterone, reducing male fertility
Increased aggression
Increased risk of heart attack + stroke
Compromised liver and kidney function
Masculinization of female users
Glucocorticoids + stress
Stressor: a stimulus that challenges the body’s homeostasis and triggers arousal
Stress response: physiological and behavioral arousal to handle stress
Activating stress response:
Fast acting → primes body immediately for fight-or-flight (epinephrine)
Slow-acting → both mobilizes the body’s resources to confront a stressor and repairs a stress-related damage (cortisol)
Activating stress response → fast-acting pathway
Hypothalamus sends neural message through spinal cord
Sympathetic division of ANS Is activated to stimulate the medulla of the adrenal gland
Adrenal medulla releases epinephrine into circulatory system
Epinephrine activates body’s cells, endocrine glands, and the brain
Activating stress response → slow-acting pathway
In brain, the hypothalamus releases CRH into pituitary gland
Pituitary gland releases ACTH, which acts on the cortex of the adrenal gland
Adrenal cortex releases cortisol into circulatory system
Cortisol activates the body’s cells, endocrine glands, and the brain
Ending a stress response
Normally, stress responses are brief and turned on/off in the brain
Hippocampus is well suited to detecting cortisol in the blood and instructing the hypothalamus to reduce blood cortisol levels → too much cortisol will damage neurons in hippocampus
Cycle involving prolonged stress: increased cortisol → triggers brain damage in hippocampus → this increases release of more cortisol
Glucocorticoid receptors in relation to childhood abuse
Glucocorticoid receptor density in hippocampus of suicide victims and childhood abuse victims was lower than that of control subjects
Decrease in receptors and glucocorticoid mRNA suggests that childhood abuse induces epigenetic changes in the expression of glucocorticoid genes
Decrease in glucocorticoid receptors presumably renders the hippocampus less able to end stress responses
