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Definition
Provides well-organized & appropriate set of autonomic, endocrine, somatic responses via:
Control over autonomic system
Control over endocrine system (control over entire endocrine system)
Coordination of certain species-specific behaviors
Primary output of limbic brain
Site of primary action or side effects (SEs) of some psychotropic drugs |
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Origin of DA (dopaminergic) pathway primarily to striatum of the basal ganglia (nigrostriatal pathway)
When 90% of DA cells die here, get Parkinson’s disease
A lot of psychotropics can cause parkinsonism (blocking dopaminergic neurons) |
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Definition
Dopaminergic neurons that project to:
Limbic system including nucleus accumbens (mesolimbic pathway: main reward pathway)
Too much dopamine can cause psychosis
Reward system
Cortex (mesocortical pathway) |
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Controls complex movements, posture, muscle tone, gait, visuomotor coordination
Ataxia (loss of coordination, balance) caused by alcohol intoxication and/or as side effect of some drugs (ex. Depakote). |
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Located from medulla through midbrain (nine of them)
Project to hippocampus, hypothalamus, limbic system and cortex
Mood (depressive disorders)
Anxiety disorders
Produces activated, waking EEG when animal moves
Also project to spinal cord to modulate reflexes (including sexual) and pain (although less than NE) |
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Definition
Mainly fibers from cerebellum
Neuron cell bodies of the locus coeruleus (makes norepinephrin/noradranalin).
Origin of norepinephrine (NE) system that projects to entire cortex
Activates cortex for alertness, responsiveness to novel stimuli, response to stressful stimuli (especially fear)
At times, produces positive feelings of reward, helps maintain emotional tone & inhibits pain |
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Term
| Reticular activating system (RAS |
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Definition
Starts here & runs through midbrain
Involved in arousal from sleep & waking through output to neocortex, diencephalon
Injury to this area (especially mid brain) leads to problems with arousal and staying awake; coma |
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Definition
Contains neurons & tracts
Controls
Breathing
Cardiovascular system
Emesis (vomiting), common side effect to psychotropics/SSRI’s |
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Performs integrative functions regulating respiration, cardiovascular activity & consciousness (especially critical in regards to drugs of abuse).
Coordinates reflexes & simple behaviors mediated by cranial nerves. |
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Consists of medulla, pons, midbrain
Acts as conduit for ascending & descending tracts between spinal cord and thalamus, cerebellum, & cortex |
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Located rostral to brainstem
Two main structures are
Thalamus
Hypothalamus: keeping homeostasis |
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Definition
Primary function is homeostasis/regulation of:
Water/electrolyte balance
Food intake (hunger, satiety)
Temperature (sweating, shivering)
Autonomic activity (blood pressure, rate/force of heart beat, respiratory rate/depth, digestive tract motility, etc.)
Sleep-wake cycle/circadian rhythmicity
General body metabolism |
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Term
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Definition
The “switchboard of the brain”
Transmits signals from all senses to cortex.
Olfaction mainly bypasses thalamus.
Types of information handled
Sensory
Motor
Integrative
Regulatory (from diffuse projecting nuclei: wake up or be alert information) |
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Helps to select which sensory & motor information will be allowed to pass to and from cortex and in what sequence.
Its “filtering” function may fail in schizophrenia causing poor signal-to-noise ratio. Possibly similar problem in autism.
Critical for cognitive functioning & coordinating activation including timing & coordination of complex problem solving |
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Definition
get information from cortex, modulate that information, and then modulate frontal cortex via thalamus.
Such modulation results in either increased or decreased excitation of frontal cortex.
Affects force/rate/amount of activity of muscles, including initiation & control of movement
Involved in subconscious habits, motor skills (along with cerebellum) |
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Definition
Comprised of subcortical & cortical structures that encircle brainstem, thalamus, basal ganglia
Subcortical portion involved with subconscious, fast responses to stimuli with positive or negative values
Cortical portion mediates conscious feelings
Important for survival of species, including motivation, emotion, memory (libido, memory, fear) |
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Definition
Learning emotional significance of stimuli, particularly with biological significance
Presence of food, water, salt, mates, rivals
Prosody (emotion someone expresses with/nothing to do with content) & facial expressions (particularly fear, anger, sadness) |
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Responding to innate fears & learning of new fears (conditioning)
The most important structure in brain for fear
Involved with other emotion as well |
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Definition
Coordinates emotional responses
Autonomic & endocrine responses via output to hypothalamus, brainstem
Defensive behavior via output to brainstem
Conscious awareness via output to prefrontal cortex, cingulate |
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Major role in craving, pleasure, addiction
Brain response to natural reinforcers & recreational drugs associated with elevated levels of extracellular dopamine in NA |
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Term
| Dorsolateral prefrontal cortex |
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Definition
Conceptualizing & maintaining goals and allocating attentional resources accordingly
Helps one focus on task at hand according to an internal plan & to avoid being distracted by stimuli (not being “pulled to the stimulus”)
Planning overall sequences & contingency planning |
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Term
| Dorsolateral Prefrontal Cortex |
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Definition
Maintaining & shifting set (adapting to novelty, cognitive flexibility)
Learning from experience based on previous behavior
Regulating behavior based on current environmental stimuli |
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| Dorsolateral Prefrontal Cortex |
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Definition
Suppressing routine responses in favor of a novel response that is required or more appropriate for a given situation
Developing strategies for solving complex problems
Abstract thinking
Time estimation
Episodic memory of place & time of autobiographical information |
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Term
| Dorsolateral Prefrontal Cortex |
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Definition
Executive component of working memory
Allows one to be free from immediate demands of environment by holding information in memory long enough to either store, manipulate, or act on it
Requires retrieval of stored memories, which critically depends on ______ although other regions (e.g., hippocampus) are also involved |
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| Dorsolateral Prefrontal Cortex |
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Definition
| allows one to act, based on internally generated rules & plans, reflection & judgment, historical information, and abstract themes common to different situations |
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| Also called lateral orbitofrontal cortex or inferior prefrontal cortex |
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Definition
Dysfunction may cause:
Disinhibition
Obsessions, compulsions
Decreased awareness of emotional states in self & others
Difficulty perceiving & producing prosody (especially with dysfunction in right hemisphere)
Decreased empathy & concern for social rules |
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Definition
| Disinhibition seen with dysfunction of OFC can also manifest as hyperactivity/impulsivity during ADHD, suicidality during depression, or risk-taking or pressured speech during mania |
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Term
| Ventromedial Prefrontal Cortex |
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Definition
Involved in motivation & emotional regulation, including the extinction of conditioned fear
Inefficient processing (under- or over-activation) may produce sxs of depression (depressed mood, excessive guilt, feelings of worthlessness, apathy, decreased social interaction, psychomotor retardation) or mania (elevated/irritable mood). |
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| Anterior Cingulate Cortex |
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Definition
| Involved with conscious emotion (feelings), attention |
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Definition
Ventral portion plays role in emotions (negative consequences, depression, anxiety, fear).
Detects mismatch between expectations & real-world outcomes
Anticipates negative consequences when mistake is made
Negative emotion that usually accompanies pain occurs here. |
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Term
| Autonomic Nervous System (ANS) |
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Definition
Involved in subconscious, homeostatic processes to maintain stable internal environment
Regulates cardiovascular, respiratory, digestive, urinary, reproductive systems
Innervates smooth (esophogus, glands, etc.) and cardiac muscle
Glandular epithelium |
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Term
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Definition
Viscera are influenced by two interdependent systems
Neural (autonomic)
Responses fast to develop but are short term
Endocrine
Responses slow to develop but are prolonged
Both under control of CNS (primarily hypothalamus)
Both affected by emotional factors & sensory input from inside & outside body |
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Term
| Sympathetic Nervous System |
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Definition
Fight or flight”
Conditions of extreme excitement or exertion bring about en masse activation of sympathetic outflow
heart rate
blood pressure
blood flow to skeletal muscles
blood glucose level
sweating
pupil diameter |
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Term
| Sympathetic Nervous System |
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Definition
Concurrent activities
gut motility
digestive gland secretion
blood flow to abdominal viscera, skin
Thus, SNS generally acts in a global, nonselective manner
Releases norepinephrine |
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Term
| Parasympathetic Nervous System (PNS) |
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Definition
- “Rest and digest”
-effects are localized
- Releases acetylcholine |
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Term
| Functional and Chemical Coding of the ANS |
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Definition
SNS uses norepinephrine (NE)
PNS uses acetylcholine (ACh)
Whether these transmitters are excitatory or inhibitory depends on type of receptor at target organ. |
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| What the body does to the drug |
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Definition
| What the drug does to the body |
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Definition
Safest and easiest route
Must pass through GI tract & enter portal circulation 1st-pass metabolism (metabolized in intestine, liver, and finally the brain). 2nd pass will go through liver again, and if there is some left, it will go to brain again.
≈ 60 min’s depending lipid solubility |
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| 50% by passes 1st pass/liver |
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Transdermal (through skin)
Transmucusal - nasal, lungs
Sec’s (Seconds) due to largest surface area and avoidance of 1st-pass metabolism
Vaginal
Intrauterine
Otic (Ear)
Ophthalmic (Eye) |
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Term
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Definition
Subcutaneous (SC, or SQ) (skin, ex. PPD)
Hrs-days/months
Intramuscular (IM) (ex. flu)
≈ 15 min’s
Intravenous (IV), Intra-arterial (IA)
Secs |
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| Injected into CSF, into lumbar cistern |
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| Release of drug from its dosage form |
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| Movement of drug from administration site into the blood |
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| Process through which drug is transferred from intra-vascular to extra-vascular space |
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Definition
| Transformation of drug into compounds which are easier to eliminate |
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Definition
| Elimination of drug or metabolite via renal, biliary or pulmonary processes |
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| 5 stages of Pharmacokinetics |
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Definition
Liberation:
Absorption:
Distribution:
Metabolism:
Excretion: |
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Definition
| mainly cytochrome P450 enzymes inactivate (usually) drug |
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Definition
| other enzymes make metabolites or (makes) drug more soluable easier to excrete |
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| a monogenetic trait in a population in at least 2 phenotypes/genotypes, neither of which is < 1% |
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Term
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Definition
| system in liver is main system of isoenzymes (enzymes with different forms) that inactivates drugs. |
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| Most important enzymes in degrading drugs are 1A2, 2C9, 2C19, 2D6 (30%), 3A4 (55%). |
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Definition
Individuals vary in level of these and, therefore, in ability to metabolize a given drug.
Differences of number of these molecules can be >10,000 fold! |
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| Age (elderly) Variability |
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Definition
| usually 2x as sensitive to drugs, thus Docs should prescribe ½ the normal dose. |
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Definition
generally less sensitive due to
greater dilution in body fluids |
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Definition
may have more sensitive receptors.
Possible hormone interactions in females
Combined w/ pharmacokinetic factors, ________may be twice as sensitive as _______. |
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| Drug-Drug interactions (DDIs) |
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Definition
| account for over 7,000 deaths annually in the U.S. |
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Definition
2 drugs, same effect
Synergistic effects
Ex. Thyroid hormone added to antidepressant |
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| Antagonistic drug effects |
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Definition
| Can lead to decreased therapeutic effect |
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Definition
One drug (or food) may alter absorption of another
One drug may alter protein binding.
(Can reduce binding proteins and increase free drug molecules which can go through BBB) |
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Definition
Drug A usually binds to CYP enzyme and be metabolized. (Drug A is a CYP-substrate).
Drug B blocks the site and doesn’t allow A to be metabolized Drug A entering circulation “un-metabolized.” (Drug B is termed a CYP-inhibitor.)
This plasma levels of the substrate Drug A.
DDI occurs almost immediately, within hours to days & can toxicity.
It doesn’t matter which drug is added first. |
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Term
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Definition
Drug A expects to bind to CYP enzyme and be metabolized. (Drug A is a CYP-substrate).
Drug C binds to enzyme and sends a message to nucleus to make more enzyme levels of enzyme and increasing metabolism of A concentration of A in circulation drug effects.
Takes days to weeks.
Will take some time to develop if drug C is added second.
Will occur immediately if drug C already present for several days. |
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Term
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Definition
Sites of functional contact between neurons.
Consist of
Presynaptic membrane w/ active zone
Synaptic cleft containing proteins & scaffolding/molecular forms of “synaptic glue” to reinforce connection between neurons
Postsynaptic membrane w/ receptors |
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| neuron’s lipid-bilayer membrane. |
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Definition
| Most molecules, including ions, cannot cross because they are charged or not sufficiently lipophillic. |
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Definition
Allow movement of ions across membrane through a gate that opens when neurotransmitter binds
Rapid change in membrane potential (msec’s)
Mediate fast behavior |
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Definition
Involved in signal transduction cascades (do not just let things in and out)
Alter internal chemistry
Can modulate ion channels
Can result in alteration of protein synthesis via effects on gene transcription |
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Term
| common type of “Metabotropic” receptor is the G protein-coupled receptor |
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Definition
Couples a neurotransmitter (1st messenger) to an effector protein via a G Protein (guanosine
phosphate binding protein) attached to the receptor |
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Term
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Definition
| It may activate an enzyme (speed a chemical reaction) or attach to an ionic channel. The enzyme can activate a second messenger, which in turn can activate other enzymes resulting in a transduction cascade that can affect many chemical reactions. |
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Definition
| affect DNA resulting in change in production of proteins |
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| G Protein-Coupled Receptors |
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Definition
Acetylcholine (Ach) to muscarinic receptor (not nicitinic receptors which would be ionotropic)
Dopamine (DA)
Norepinephrine (NE)
Epinephrine (E)
Serotonin (5-HT), except to 5-HT3 receptor
Glutamate (Glu) to GLU metabotropic receptor
Histamine
GABA to GABAB receptor |
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Term
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Definition
| can enter neuron through an ionotropic receptor and serve as a 2nd messenger, eventually resulting in gene transcription |
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Term
| type of “metabotropic” receptor is an intracellular receptor that binds to a lipid-soluable neurotransmitter that has crossed the membrane |
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Definition
Nuclear hormone receptors bind to steroids (corticosteroids, mineralcorticoids, sex steroids, vitamin D), thyroid hormone
Hormone/nuclear receptor complex travels to nucleus, resulting in gene transcription |
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| Characteristics of metabotropic receptors |
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Definition
Tremendous amplification of signal
Flexibility & diversity of responses
Can affect ion channels, membrane potentials, enzyme activity, gene transcription (protein production)
Diversity of receptor subtypes |
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Definition
are slower (tens of milliseconds, seconds) & last longer (seconds, hours, days or longer)
modulate synaptic actions & behavior by altering excitability of neurons & strength of synaptic connections (i.e., modulate strength & efficiency of fast-acting transmission)
Affect how neurons respond to input from other neurons, including efficiency of cognitive processes |
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