Neurotransmitters and Receptors Flashcards
What are the major neurotransmitters found in the reward circuit?
Dopamine
Glutamate
GABA
What is a catecholamine?
Monoamine neurotransmitters made by the adrenal gland
What is dopamine the primary driver of?
The reward circuit
Where is dopamine particularly important?
The second phase of the reward circuit, VTA -> NAc
What neurotransmitters are catecholamines?
Dopamine
Norepinephrine
Where is a major source of NE projections in the brain?
From the locus coeruleus
What neurotransmitter plays a big role in stress-induced relapse?
Norepinephrine
What is GABA?
A major inhibitory neurotransmitter
What is GABA central to?
To disinhibitory mechanisms of reward
What is glutamate?
An amino acid
What does glutamate play a major role in?
Cue-triggered relapse
LTP/LTD plasticity
What is serotonin?
Monoamine indole
Where is a major source of serotonin found?
In the raphe nuclei
There is a link between low serotonin and what?
Impulsivity and violence in addicts
How many genes are there in dopamine receptors?
5
What do D1-like type DA receptors do?
Increases cytoplasmic [cAMP] via adenylyl cyclase
Stimulatory
What do D2-like type DA receptors do?
Decreases cytoplasmic [cAMP] via adenylyl cyclase
Inhibitory
What are D1-like type DA receptors responsible for?
Cognition
What are D2-like type DA receptors responsible for?
Locomotion
What is translational research?
Conducting research that translates into benefiting people
e.g. animal testing
What does the effort exerted to self-administer drugs in animals relate to?
The degree of reward experienced
What does pairing of an environment with stimulation of VTA DA-ergic projections cause?
Immediate place preference that will last for several days
What does it mean if the animal spends time in the drug-paired chamber?
They are exhibiting drug-seeking behaviour
What is microdialysis used for?
To measure neurotransmitter levels in specific nuclei directly
What does control hedonic tone look like?
Tonic DA release
There is a consistent baseline level of dopamine release
How do addictive drugs affect hedonic tone?
Induce phasic (bursts) of dopamine firing (release) in the NAc
Why can dopamine antagonists be used in therapy?
They are negative reinforcers that enhance behaviours to reduce administration
What does a low point in fluctuating dopamine levels predict?
The next self-administered dose
What happens when you develop tolerance against a drug?
Lowered elevation of hedonic tone during chronic use
Need higher and higher doses just to feel normal
What are AMPARs?
AMPA receptors for fast, excitatory transmission
What are the characteristics of AMPARs?
Ionotropic
Form tetramers
C-terminus forms intracellular scaffolds
4 genes
What do AMPARs play a major role in?
Long-term depression
How many genes and protein units are in NMDARs?
7 genes (1 GluN1, 4 GluN2, 2 GluN3)
7 protein subunits
What are NMDARs activated by?
Co-activated by Glu and Ser/Gly
What type of receptors are NMDARs?
Ionotropic
What are NMDARs critical for?
For synaptic plasticity (LTP/LTD)
What is NMDAR signalling dependent on?
Ca2+
What is excitotoxicity?
Cooking neurons
What type of receptors are glutamate receptors?
Metabotropic
How many genes are in glutamate receptors?
8 genes
What are glutamate receptors involved in?
Synaptic plasticity
What do group I Gq-linked receptors do?
Increase excitotoxicity risk
What do group II/III Gi/o-linked receptors do?
Decrease excitotoxicity risk
What can increased calcium lead to?
Increased risk of excitotoxicity
What is LTP?
Strengthening of synaptic transmission between two neurons downstream of glutamate receptors
What are the 4 things associated with LTP?
Specificity
Associativity
Cooperativity
Persistence
What is specificity?
Sites of LTP are confined to specific contact sites
What is associativity?
Strong stimulation through one pathway will induce LTP for weak pathways at the same site
What is cooperativity?
Many weak stimuli can induce LTP; constructive interference
What is persistence?
Potentiation lasts minutes, weeks, and months; unique to LTP
What is LTD?
Weakening of synaptic transmission between two neurons
What does the phasic firing of VTA DA-ergic neurons generate?
A learning signal when an unexpected reward occurs
What happens when a reward becomes fully predictable?
DA-ergic neurons are no longer triggered and learning ceases
What does the learning signal lead to in the context of addictive drugs?
Drug adaptive behaviours leading to compulsive drug intake at the expense of all other behaviours
What does NE innervation activate?
Sympathetic responses which plays a major role in stress-induced drug relapse
Are drugs that target serotonin receptors more or less addictive?
Less
What does ACh activate?
Parasympathetic responses which plays a major role in learning and memory circuits
What is acute use?
One use/month, no lingering effects of use
What is chronic use?
More than a month of use
What happens to tissue over long-term periods of addiction?
Can become dysfunctional
