PSYCH 454 - Exam I
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Drug _______ refers to the specific molecular changes produced by a drug when it binds to a particular target site or receptor while drug ______ refers to alterations in physiological or psychological functions induced by a drug.
_____________ refers to the factors that contribute to bioavailability (e.g., absorption, binding, excretion) of a drug while ___________ refers to the physiological and biochemical interaction of drugs with target tissue (i.e., mechanism of action).
When drugs are _______________ they are more easily absorbed and distributed throughout the body.
The ______________ of a drug refers to the difference between the ED50 and the TD50.
What are the three ways that drugs can interact?
- Physiological antagonism
- Additive effects
What are the three different forms of tolerance that were discussed in class?
- Tolerance due to increased amounts of enzymes to break the drug down
- Tolerance due to up or down regulation of the number of receptors the drug can bind to
- Tolerance due to taking the drug in the same location/manner (learned context dependence)
What is the difference between a competitive antagonist and a non-competitive antagonist? Which reduces potentcy? Which reduces efficacy?
A competitive antagonist binds to the same spot on a receptor as the receptor agonist reducing potency (you need more of the drug to outcompete the agonist) while a non-competitive antagonist binds to a different spot on the receptor and reduces potentcy (no matter how much of the drug you take you won't get as much of the effect because some of the receptors are blocked by the antagonist)
Agonists _________ a response, bind with ____ affinity and have ____ efficacy. Chronic use leads to ______ regulation of the number of available receptors.
Initiate; high; high; down
Antagonists _________ a response, bind with ____ affinity and have ____ efficacy. Chronic use leads to ______ regulation of the number of available receptors.
Inhibit; high; low; up
What are three ways that a drug can be inactivated?
- Drugs can be chemically altered by enzyme catalyzed reactions
- Non-synthetic modification (break down the drug via hydrolysis, oxidation, or reduction)
- Synthetic modification (add a small molecule to the drug making it inactive)
What are four factors that affect the rate of drug metabolism?
- Enzyme induction
- Enzyme inhibition
- Drug competition
- Individual differences
Show that you understand the three different planes used to examine the brain.
Give the function for each of the following brain areas.
Ventral Tegmental Area
- Vital functions
- Arousal, attention
- Coordination, motor learning
- Relay station
- Endocrine control
- Emotional response
- Motor control
Describe the key finding of Otto Loewi's experiment as well as how he figured it out.
Synaptic signalling is a chemical process
What are three ways that released neurotransmitters can be inactivated?
- Enzymatic breakdown in the synaptic cleft
- Reuptake by pre-synaptic neuron
- Reuptake by surroudning glial cells
Explain the function of autoreceptors as well as how they work.
Autoreceptors are located on the pre-synaptic cell and will bind neurotransmitter when there is a lot in the synapse, this inhibits further release of neurotransmitter into the synaptic cleft.
Compare and contrast the differences between metabotropic and ionotropic receptors
- Single protein w/ 7 membrane spanning domains
- Binding of neurotransmitter causes activation of G-protein
- G- protein activates other ion channels and effector enzymes
- Effector enzymes release 2nd messengers
- Have slower but more global effects
- Composed of 4-5 subunits
- Binding of neurotransmitter allows passage of ions through the receptor
- Have fast limited effects
Neurotrophic factors bind to ______________ receptors promoting neuron growth. The most common neurotrophic factor of the brain is ________ and the most common neurotrophic factors of the periphery is ___________
- Tyrosine kinase receptors
- Brain-derived growth factor (trkA)
- Nerve growth factor (trkB)
What three things discussed in class are most likely to lead to relapse?
- Conditioned cues
- Small quantities of the abused drug
Sensitization to drugs of abuse is intiated in _________ and reinforced in the __________
- Ventral tegmental area
- Nucleus accumbens
Give the enzymes for each conversion in the synthesis of dopamine and norepinephrine, which step in this synthesis is the rate limiting step?
Tyrosine is converted to L-DOPA by ____________
L-DOPA is converted to dopamine by____________
Dopamine is converted to norepinephrine by_______
- Tyrosine hydroxylase (*rate-limiting)
- Aromatic amino acid decarboxylase
- Dopamine Beta-hydroxylase
What four neurotransmitters are classified as monoamines and which protein is responsible for transporting synthesized monoamines into vessicles in the pre-synaptic cell? What research drug blocks the activity of this protein?
Dopamine, norepinephrine, epinephrine, serotonin, vesicular monoamine transporter, reserpine
How do autoreceptors inhibit further release of neurotransmitter?
Prevent additional calcium from entering the cell
Norepinephrine and dopamine are broken down in the synaptic cleft by which two enzymes?
- Monoamine Oxidase
What are the three dopaminergic pathways?
Nigrostriatal, mesocortical, mesolimbic
The two families of dopamine receptors are the __ family and the __ family. Both receptors are ____________ and __ inhibits cAMP while __ stimulates cAMP
D1 and D2, metabotropic, D2, D1
Dopaminergic neurons signal ______________ and with time learn to signal ____________________.
unexpected reward, a stimulus predictive of reward
There are roughly 3,000 noradrenergic neurons in the brain, all of which are located in the __________ of the ____. These few neurons project to the ___________.
Locus coeruleus, pons, entire brain
In class we discussed four types of noradrenergic receptors. Briefly describe what each type does.
- The Beta-1 and Beta-2 receptors stimulate cAMP
- The Alpah-2 receptor inhibits cAMP
- The Alpha-1 receptors uses phosphoinosidate as its 2nd messenger instead of cAMP and this increases Ca2+ in the post-synaptic cell (hyper-polarization, inhibitory)
Acetylcholine is broken down by the enzyme ____________, this enzyme must break down acetylcholine quickly (especially at the neuromuscular junction) to allow for _____________
Acetylcholinesterase; precise control of muscles
What are the two types of acetylcholine receptors? What type of receptor is each (ionotropic or metabotrobic; excitatory or inhibitory)?
- Nicotinic receptor (Ionotropic-excitatory)
- Muscarinic receptor (Metabotropic - inhibitory)
Tryptophan is converted to 5-HTP by the enzyme _______________ and 5-HTP is converted to serotonin by the enzyme _____________. The rate-limiting step is the conversion from ___________ to _____________.
Tryptophan hydroxylase; Aromatic amino acid decarboxylase; Tryptophan to 5-HTP
The 5-HT1A serotonin receptor involved in _________, __________, and __________. Activation of this receptor produces and overall _______ response by ________ cAMP and opening __________.
regulation of eating, anxiety, and regulation of tempurature
inhibitory, inhibiting, potassium channels
Glutamate clearence is accomplished by five membrane transporter proteins and the enzyme ______________ which converts glutamate to __________. Why is this process so important?
- Glutamine synthetase, glutamine
- Glutamate is the major exictatory NT of the brain and if it is present in high quantity it is neurotoxic as it leads to over-excitation and seizure.
Name and describe the two primary glutamate receptors in the brain.
AMPA is ionotropic and allows for fast excitatory responses
NMDA is metabotropic and complicated (see other flashcard)
The NMDA receptor is unlike many other receptors, when open it allows ___ and ___ into the neuron, however, for this receptor to open it must bind ______ AND ______. Furthermore, the ions mentioned above will not enter because of a ___ block that will only be removed when the cell has been sufficiently depolarized by activation of ________.
Na+ and Ca2+; glutamate AND glycine; Mg2+; AMPA receptors
Explain the role of the NMDA receptor in long-term potentiation.
A single action potential will activate the AMPA receptor, and the NMDA receptor will only open when multiple action potentials occur. Furthermore, the NMDA receptor allows Ca2+ into the cell which activates CaMKII, this protein makes the AMPA receptors more sensitive to glutamate by phosphorylating them and adding more of them
GABA is broken down into succinate and _______ by the enzyme ____________.
Glutamate; GABA aminotransferase
The ionotropic GABA receptor is called ________ and causes inhibition by allowing _____ into the cell promoting ____________; the metabotropic GABA receptor is called __________ and causes inhibition by allowing ____ out of the cell and inhibiting formation of _______.
GABAA; Cl-; hyperpolarization
GABAB; K+; cAMP
Induction of long-term potentiation is NMDA _________ while expression of LTP is NMDA __________
NMDA receptors act as "________________" for two events. Due to this these receptors are important for pairing __________ or a ________ and a _______; this process can be summarized as ______________ and is thought to occur primarily in the ____________.
Coincedence detectors; two stimuli; stimulus; response; associative learning; hippocampus
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