07 | Addiction Flashcards
The reward pathway is also known as ___. It is made up of…
- cortical limbic system pathway
2. VTA-NAc-FC
Major sources of DA in the brain
- VTA (reward)
2. SN (voluntary movement)
Effect of opioids on DA
inhibit GABA ⇒ ↓ inhibition of DA release ⇒ more DA
Effect of nicotine on DA
↑ dopaminergic innervation
Effect of cocaine, amphetamines on DA
↑ DA release, ↓ DAT ⇒ more dopaminergic innervation
Neuron composition of VTA
60% DA
40% GABA
DA on NAc has what effect?
reward & reinforcement
DA on PFC has what effect?
exclusive function (loss of control)
DA on hippocampus has what effect?
memory
DA on amygdala has what effect?
emotions
What 2 things are needed for withdrawal response?
- Stress
2. DA
What was the experimental procedure that determined the relationship between stress and reward pathways? What was the result?
double labelling + in situ hybridization
In drug users, neuroadaptation of VTA DA neurons lead them to express CRF
What happens to synaptic plasticity in drug addiction?
- Promote LTP of dopamine (reward) pathways
- Promote LTD of GABA (inhibitory) pathways
- Loss of synaptic plasticity in NAc → linked to inability to control drug intake
How does cocaine promote LTP in certain pathways? What is 1 short-term response?
↑ AMPA on VTA DA neurons⇒ stronger EPSP (LTP)
↑ dendritic spine density in VTA DA neurons ⇒ ↑ possibility of forming synapses (this is only for short-term response)
Cocaine-induced LTP can be blocked by…
MK-801 (NMDA blocker)
Which subunits of AMPA-R are not likely involved in LTP response to cocaine?
GluA1 and GluA2
What eventually stops the ↑ AMPA LTP response?
mGluR1 (Ro 67)
What is Ro 67?
mGluR1 activator
LTP response is _synaptic, while LTD is _synaptic
- pre
2. post
2 ways to induce LTD at VTA GABA-DA synapses
- LFS
2. Morphine
Mechanism used by LFS to cause LTD
decrease number and conductance of GABA(A)-R
Does LTD depend on NMDA-Rs?
No
Actions of morphine to cause LTD
- Prevent LFS-LTD
2. induces its own LTD (unclear)
Drugs that can induce LTD
nicotine, morphine, cocaine, alcohol
How can addictive behaviors be prevented (has to do with GABA)
increase GABA innervation
List 2 NMDA-R blockers
- MK-801
2. APV
What is the “switch” between addicted and non-addicted states?
BDNF
What defines the sensitivity limits of sensory stimuli?
sensory receptors
Define: adequate stimulus
the specific stimulus that a receptor responds to best
Define: transduction
changing adequate stimulus to electrical signal (receptor potential)
Adequate stimulus is a property of the ___
receptor
Receptor potential is recognized by CNS by:
- Anatomical position
2. sensory ending
Area of brain that controls smell
olfactory cortex
area of brain that controls memories
temporal cortical region
Damage to temporal cortical region has what effect on smell?
Prevents identification of smells, but you can still smell things
Mammals have how many axons projecting to the olfactory bulb?
100 000
Mucus in the nasal cavity is __ thick and replaced every __ min.
50 um
10 min
Olfactory receptors are replaced every __ months. New receptors originate from __.
1-2 months
basal cells in olfactory epithelium
What is the only area in the brain that generates new neurons throughout life?
Olfactory bulb
Zones in the olfactory epithelium are regulated by…
expression of different receptor genes
In rats, the olfactory epithelium rests on top of __
turbinates
The same zone in the olfactory epithelium projects to…
a single pair of medial & lateral glomeruli in the olfactory bulb
What is in the limbic system?
- amygdala
- entorhinal cortex
- hippocampus
- subiculum
From the olfactory bulb, projections are made to…
- Limbic system (motivation, emotion, memory)
2. Thalamus & FC (recognition)
Which currents are responsible for olfactory conductance?
inward K current, odorant current (open non-selective cation channels)
The K current causes __ depolarization, but the odorant current causes __ depolarization
- initial
2. prolonged (2nd messenger)
Non-selective cation channels opened by odorant lets in __ > __»_space; __
Ca > Na»_space; K
which G protein is associated with odorant receptors?
G(olf)
Mechanisms of G(olf)?
- -> more AC -> more cAMP -> open non-selective cation channels -> more Ca
- -> IP3 -> DAG -> release Ca from intracellular stores
What are the 2 mechanisms to cause depolarization in ORN?
- Ca influx due to G(olf)
2. Ca-gated Cl current
What is the disease when there is no smell or reduced smell?
Anosmia
Causes of anosmia
- head injury
- virus
- congenital
- consequence of other disorder
3 compartments of the cochlea
- Scala media
- Scala vestibuli
- Scala tympani
Composition of scala media
- Endolymph
- High K, low Na, low Ca
- Concentration is actively maintained
Composition of scala vestibuli
perilymph
Composition of scala tympani
- perilymph
- similar to CSF
What are the membranes found in the cochlea? What to they separate?
Reissner’s membrane: media + vestibuli
Basilar membrane: media + tympani
Inner layer of hair cells is responsible for ___ signals, and outer hair cells are responsible for ___ signals
- afferent
2. efferent
Hair cells sense vibration from ___ and ___ membranes
Basilar, tectorial
How to hair cells cause depolarization and signal propagation?
movement -> open tip links -> K influx from endolymph -> depolarization -> open v-gated Ca channels -> vesicle release
Which ways does hair cells bend to cause hyperpolarization/depolarization?
- toward kinocilium = depolarization
- away from kinocilium = hyperpolarization
What kind of specialized synapse does hair cells have? Which NT is used?
- Ribbon synapse
- Glu
What # is the auditory nerve?
VIII
What is the pathway after nerve VIII?
nerve VIII -> medulla -> inferior colliculus (midbrain) -> medial geniculate nucleus (thalamus) -> auditory cortex
Which lobe is the auditory cortex located in?
temporal
Explain electromotility
depolarization cause hair cells to shorten, while hyperpolarization cause hair cells to lengthen. Movement of the hair cells also contribute to vibrations.
Electromotility is mediated by…
prestin (v-dependent motor protein that is coupled to the exoskeleton)
Tonotropic organization of auditory neurons
Different neurons in the auditory cortex responds to different frequencies
___ is the frequency that a neuron responds best to
characteristic frequency