Plasticity Flashcards
(23 cards)
How is glutamate synthesised?
from glutamine via glutaminase
What are the types of glutamate vesicles?
VGLUT1
VGLUT2
VGLUT3
What are the implications of VGLUT1 and where are they found?
knockouts die ~ 3 weeks after birth
cortex and hippocampus
What are the implications of VGLUT2 and where are they found?
knockouts die at birth
subcortical structures
What are the implications of VGLUT3 and where are they found?
knockouts survive but are deaf
How is glutamate inactivated?
by excitatory amino acid transporters 1 and 2
uptake glutamate into astrocytes
glutamate + glutamate synthetase = glutamine
What are the types of glut receptor?
ionotropic; AMPA, NMDA, Kainate
metabotropic; mGluR1-8
What are the mechanisms of ionotropic receptors?
AMPA; Na+
NMDA; Na+ and Ca2+ (has a sodium block)
kainate; Na+
What are the mechanisms of metabotropic receptors?
inhibit cAMP formation
activate second messenger system
What are the major reward pathways and which NT mediates it?
VTA - NAcc via dopamine
PFC - VTA via glutamate
What is drug sensitisation?
with each dose there is an increased response to the drug; measured by locomotion
7 day withdrawal then re-exposure elicits greatest hyperactive response
How can relapse be modelled in animals?
train rats to self-administer drugs using a lever
drug-associated cue; light (e.g. smoke/needle)
after protracted withdrawal re-exposure to the associated cue induces high active lever presses
How can drugs affect dendritic spines?
repeated cocaine = increased accumbal spine density, length and branching
spine density only altered when cocaine given in novel environment
spine density altered by drug not instrumental learning
What is the structure and function of spines?
spines protrude from dendrites
AMPAR and NMDAR are located on spines
spine head size correlates with number AMPAR
spine density correlates with connectivity
In what circumstances can spines be abnormal?
mental disorder patients and drug addicts show abnormal density and morphology
What are the limitations of spine morphology research?
could be silent synapses
could be the same amount of connectivity
What are the effects of drugs on accumbal dendritic morphology?
increased dendritic branching, length and density
SA of drugs not natural rewards
dose-dependent increases that dissipate; role in initial risk of relapse
What are the effects of drugs on VTA synaptic potentiation?
transient increases in AMPAR + locomotion; EA
potentiated AMPAR following cocaine but not natural reward; SA
only a single exposure is requires
transient implicates role in initiation of sensitisation
What are the effects of drugs on NAcc synaptic potentiation?
behavioural sensitisation + increased AMPAR; develops as a function of withdrawal
repeated exposures required
insertion of GluR2-lacking AMPAR; pass Ca2+
- Naspm inactive GluR2-lacking AMPAR diminished cocaine-seeking; GluR2-lacking AMPAR responsible for cocaine-seeking
impaired NMDAR-mediated LTD
What are the effects of drugs on accumbal neuronal ensembles?
increased ensemble activity and context-specific psychomotor sensitisation
specific ensembles are responsible for encoding the association between drug and administration environment; Daun02 inactivation
Which addiction-like behaviours can be measured in the rat?
motivation; progressive ratio
use despite consequences; footshock
difficulty limiting intake; seeking after drug removed
What can addiction-like behaviour experiments in rats tell us?
similar number of rats become addicted as humans ~20%
relapse test after period of withdrawal
‘addict-like’ rats show increased SA during long-access session
What is context-specific sensitisation?
neuronal activity and behavioural response are only sensitised in a specific context
